Scholars@Duke
Victor J. Dzau

Victor J. Dzau

James B. Duke Distinguished Professor of Medicine
Medicine, Cardiology
victor.dzau@duke.edu
Victor J. Dzau Laboratory Gsrbii # Room 4015, Duke University, Durham, NC 27710
Victor J. Dzau Laboratory, Gsrbii # Room 4015, Durham, NC 27710

Selected Publications

A Crossroads in Cardiovascular Medicine: Progress and Barriers to Impact.

Journal Article Circulation · October 21, 2025 During the past 75 years, advances in cardiovascular science and technology have significantly reduced morbidity and mortality. In 2012, Drs Nabel and Braunwald reviewed this progress in A Tale of Coronary Artery Disease and Myocardial Infarction, highligh ... Full text Link to item Cite

The Singapore Health Services and Duke University–National University of Singapore Graduate Medical School Academic Medical Center: Transforming Medicine Through Collaborative Innovation

Journal Article Academic Medicine · September 1, 2025 Singapore Health Services (SingHealth) and Duke University–National University of Singapore Graduate Medical School (Duke-NUS) established an academic partnership, which was born out of a single vision to transform medicine and improve lives. This partners ... Full text Cite

Vital Directions For Health And Health Care: Priorities For 2025.

Journal Article Health affairs (Project Hope) · February 2025 In 2016, ahead of the US presidential election, the National Academy of Medicine launched the strategic initiative Vital Directions for Health and Health Care-a series of papers on critical areas of US health care written by the nation's experts and intend ... Full text Cite

Four Opportunities To Revitalize The US Biomedical Research Enterprise.

Journal Article Health Aff (Millwood) · February 2025 The US biomedical research enterprise is renowned for its historical and ongoing scientific breakthroughs and advancements. Yet its capacity to solve complex health issues, bridge health equity gaps, and strengthen public trust is constrained by the lack o ... Full text Link to item Cite

Nucleosome repositioning in cardiac reprogramming.

Journal Article PLoS One · 2025 Early events in the reprogramming of fibroblasts to cardiac muscle cells are unclear. While various histone undergo modification and re-positioning, and these correlate with the activity of certain genes, it is unknown if these events are causal or happen ... Full text Link to item Cite

Strategic imperatives for health in the USA: a roadmap for the incoming presidential administration.

Journal Article Lancet · December 7, 2024 As the beginning of the next US presidential administration approaches, the USA faces a series of complex challenges that threaten the health of the American people and the effectiveness and sustainability of their health and health-care systems. Taking of ... Full text Link to item Cite

The impact of aging on cardiac repair and regeneration.

Journal Article J Biol Chem · September 2024 In contrast to neonates and lower organisms, the adult mammalian heart lacks any capacity to regenerate following injury. The vast majority of our understanding of cardiac regeneration is based on research in young animals. Research in aged individuals is ... Full text Link to item Cite

Health-care workforce implications of the Dobbs v Jackson Women's Health Organization decision.

Journal Article Lancet · June 22, 2024 The Dobbs v Jackson Women's Health Organization Supreme Court decision, which revoked the constitutional right to abortion in the USA, has impacted the national medical workforce. Impacts vary across states, but providers in states with restrictive abortio ... Full text Link to item Cite

Societal implications of the Dobbs v Jackson Women's Health Organization decision.

Journal Article Lancet · June 22, 2024 On June 24, 2022, the US Supreme Court's decision in Dobbs v Jackson Women's Health Organization marked the removal of the constitutional right to abortion in the USA, introducing a complex ethical and legal landscape for patients and providers. This shift ... Full text Link to item Cite

Modifying miRs for effective reprogramming of fibroblasts to cardiomyocytes.

Journal Article Mol Ther Nucleic Acids · June 11, 2024 Reprogramming scar fibroblasts into cardiomyocytes has been proposed to reverse the damage associated with myocardial infarction. However, the limited improvement in cardiac function calls for enhanced strategies. We reported enhanced efficacy of our miR r ... Full text Link to item Cite

C166 EVs potentiate miR cardiac reprogramming via miR-148a-3p.

Journal Article J Mol Cell Cardiol · May 2024 We have demonstrated that directly reprogramming cardiac fibroblasts into new cardiomyocytes via miR combo improves cardiac function in the infarcted heart. However, major challenges exist with delivery and efficacy. During a screening based approach to im ... Full text Link to item Cite

Skeletal muscle differentiation induces wide-ranging nucleosome repositioning in muscle gene promoters.

Journal Article Sci Rep · April 24, 2024 In a previous report, we demonstrated that Cbx1, PurB and Sp3 inhibited cardiac muscle differentiation by increasing nucleosome density around cardiac muscle gene promoters. Since cardiac and skeletal muscle express many of the same proteins, we asked if C ... Full text Link to item Cite

Precision Hypertension.

Journal Article Hypertension · April 2024 Hypertension affects >1 billion people worldwide. Complications of hypertension include stroke, renal failure, cardiac hypertrophy, myocardial infarction, and cardiac failure. Despite the development of various antihypertensive drugs, the number of people ... Full text Link to item Cite

RNA Therapeutics for the Cardiovascular System.

Journal Article Circulation · February 27, 2024 RNA therapeutics hold significant promise in the treatment of cardiovascular diseases. RNAs are biologically diverse and functionally specific and can be used for gain- or loss-of-function purposes. The effectiveness of mRNA-based vaccines in the recent CO ... Full text Link to item Cite

Vital directions for health & health care: An initiative of the national academy of medicine

Book · September 9, 2023 What can be more vital to each of us than our health? Yet, despite unprecedented health care spending, the U.S. health system is substantially underperforming, especially with respect to what should be possible, given current knowledge. Although the United ... Full text Cite

Preface

Book · September 9, 2023 Cite

Embed equity throughout innovation.

Journal Article Science · September 8, 2023 The social benefit of technologies is frequently unevenly realized across the United States. Rural communities, individuals with disabilities, and historically marginalized groups face out-of-reach costs or lack access to products that meet their needs. Bl ... Full text Link to item Cite

The US National Academy of Medicine.

Journal Article Am J Phys Med Rehabil · June 1, 2023 Full text Link to item Cite

Neonatal and adult cardiac fibroblasts exhibit inherent differences in cardiac regenerative capacity.

Journal Article J Biol Chem · May 2023 Directly reprogramming fibroblasts into cardiomyocytes improves cardiac function in the infarcted heart. However, the low efficacy of this approach hinders clinical applications. Unlike the adult mammalian heart, the neonatal heart has an intrinsic regener ... Full text Link to item Cite

Rig1 receptor plays a critical role in cardiac reprogramming via YY1 signaling.

Journal Article Am J Physiol Cell Physiol · April 1, 2023 We discovered that innate immunity plays an important role in the reprogramming of fibroblasts into cardiomyocytes. In this report, we define the role of a novel retinoic acid-inducible gene 1 Yin Yang 1 (Rig1:YY1) pathway. We found that fibroblast to card ... Full text Link to item Cite

Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2.

Journal Article Sci Rep · March 9, 2023 Current methods to generate cardiomyocytes from induced pluripotent stem cells (iPSc) utilize broad-spectrum pharmacological inhibitors. These methods give rise to cardiomyocytes which are typically immature. Since we have recently demonstrated that cardio ... Full text Link to item Cite

The Global Roadmap for Healthy Longevity: United States of America National Academy of Medicine Consensus Study Report, 2022

Journal Article Journal of the Economics of Ageing · February 1, 2023 In 2019, the United States of America National Academy of Medicine (NAM) charged an international, independent, and multidisciplinary commission with the development of a consensus report: “The Global Roadmap for Healthy Longevity,” to assess the challenge ... Full text Cite

Preparing for Pandemic

Chapter · January 1, 2023 Today I will review COVID-19 global response preparedness, emphasizing two things. First is the report from the Global Preparedness Monitoring Board (GPMB). Second are some important developments regarding countermeasures and vaccines, and how we are tryin ... Full text Cite

A global roadmap to seize the opportunities of healthy longevity

Journal Article Nature Aging · December 1, 2022 Full text Cite

Hospital-at-Home: Multistakeholder Considerations for Program Dissemination and Scale.

Journal Article Milbank Q · September 2022 Policy Points Hospital-at-Home (HaH) is a home-based alternative for acute care that has expanded significantly under COVID-19 regulatory flexibilities. The post-pandemic policy agenda for HaH will require consideration of multistakeholder perspectives, in ... Full text Link to item Cite

A novel Cbx1, PurB, and Sp3 complex mediates long-term silencing of tissue- and lineage-specific genes.

Journal Article J Biol Chem · June 2022 miRNA-based cellular fate reprogramming offers an opportunity to investigate the mechanisms of long-term gene silencing. To further understand how genes are silenced in a tissue-specific manner, we leveraged our miRNA-based method of reprogramming fibrobla ... Full text Link to item Cite

How Academic Health Systems Can Be Ready for the Next Pandemic.

Journal Article Acad Med · April 1, 2022 The COVID-19 pandemic created significant challenges for academic health systems (AHSs) across their tripartite mission of providing clinical care, conducting research, and educating learners. Despite these challenges, AHSs played an invaluable role in res ... Full text Link to item Cite

Translating science to medicine: The case for physician-scientists.

Journal Article Sci Transl Med · February 16, 2022 As the number of physician-scientists continues to decline, action must be taken to support them as they embark on their careers. ... Full text Link to item Cite

National plan for health workforce well-being (2022)

Book · January 1, 2022 In the United States, 54% of nurses and physicians, 60% of medical students and residents, and 61% of pharmacists have symptoms of burnout. Burnout is a long-standing issue and a fundamental barrier to professional well-being. It was further exacerbated by ... Full text Cite

Basic and Translational Research in Cardiac Repair and Regeneration: JACC State-of-the-Art Review.

Journal Article J Am Coll Cardiol · November 23, 2021 This paper aims to provide an important update on the recent preclinical and clinical trials using cell therapy strategies and engineered heart tissues for the treatment of postinfarction left ventricular remodeling and heart failure. In addition to the au ... Full text Link to item Cite

A role for Sfrp2 in cardiomyogenesis in vivo.

Journal Article Proc Natl Acad Sci U S A · August 17, 2021 Cardiomyogenesis, the process by which the body generates cardiomyocytes, is poorly understood. We have recently shown that Sfrp2 promotes cardiomyogenesis in vitro. The objective of this study was to determine if Sfrp2 would similarly promote cardiomyogen ... Full text Link to item Cite

Advancing the Learning Health System.

Journal Article N Engl J Med · July 1, 2021 Full text Link to item Cite

Urgent lessons from COVID 19: why the world needs a standing, coordinated system and sustainable financing for global research and development.

Journal Article Lancet · March 27, 2021 The research and development (R&D) ecosystem has evolved over the past decade to include pandemic infectious diseases, building on experience from multiple recent outbreaks. Outcomes of this evolution have been particularly evident during the COVID-19 pand ... Full text Link to item Cite

Bench to Bedside Discovery, Innovation, Global Health Equity, and Security: A Conversation With Victor J. Dzau, MD.

Journal Article Circulation · March 16, 2021 Dr Dzau was born in Shanghai. He received his Bachelor of Science in Biology and his MD degree from McGill University. He was a medical resident, Chief Resident, and the founding Chief of the Division of Vascular Medicine at the Peter Bent Brigham Hospital ... Full text Link to item Cite

Enhancing cardiac reprogramming via synthetic RNA oligonucleotides.

Journal Article Mol Ther Nucleic Acids · March 5, 2021 Reprogramming scar fibroblasts into new heart muscle cells has the potential to restore function to the injured heart. However, the effectiveness of reprogramming is notably low. We have recently demonstrated that the effectiveness of reprogramming fibrobl ... Full text Link to item Cite

Vital Directions For Health And Health Care: Priorities For 2021.

Journal Article Health Aff (Millwood) · February 2021 In 2016, in anticipation of the US presidential election and forthcoming new administration, the National Academy of Medicine launched a strategic initiative to marshal expert guidance on pressing health and health care priorities. Published as Vital Direc ... Full text Open Access Link to item Cite

Production of Cardiomyocytes by microRNA-Mediated Reprogramming in Optimized Reprogramming Media.

Journal Article Methods Mol Biol · 2021 There are currently no effective treatments to regenerate the heart after cardiac injury. Following cardiac injury, heart muscle cells, also known as cardiomyocytes, die in large numbers. The adult mammalian heart does not have the ability to replace these ... Full text Link to item Cite

Sequential paracrine mechanisms are necessary for the therapeutic benefits of stem cell therapy.

Journal Article Am J Physiol Cell Physiol · December 1, 2020 Stem cell injections are an attractive therapeutic tool. It has been demonstrated that injected stem cells promote tissue repair and regeneration via paracrine mechanisms. However, the effects of injected stem cells continue for far longer than they are pr ... Full text Link to item Cite

Optimizing delivery for efficient cardiac reprogramming.

Journal Article Biochem Biophys Res Commun · November 26, 2020 Following heart injury, cardiomyocytes, are lost and are not regenerated. In their place, fibroblasts invade the dead tissue where they generate a scar, which reduces cardiac function. We and others have demonstrated that combinations of specific miRNAs (m ... Full text Link to item Cite

Achieving healthy human longevity: A global grand challenge.

Journal Article Sci Transl Med · October 21, 2020 With continued advances in science and technology, there is great potential to extend our healthspan as we age. ... Full text Link to item Cite

Digital technology and COVID-19.

Journal Article Nat Med · April 2020 The past decade has allowed the development of a multitude of digital tools. Now they can be used to remediate the COVID-19 outbreak. ... Full text Link to item Cite

Time for NIH to lead on data sharing.

Journal Article Science · March 20, 2020 Full text Link to item Cite

Sox6 as a new modulator of renin expression in the kidney.

Journal Article Am J Physiol Renal Physiol · February 1, 2020 Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells that give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation, renal me ... Full text Link to item Cite

Vital Directions for Health & Health Care: The North Carolina Experience

Journal Article North Carolina Medical Journal · January 1, 2020 In 2019, the National Academy of Medicine (NAM) turned to the all-important state level to draw insights on the status of health and health care within the context of the NAM Vital Directions for Health and Health Care initiative. The NAM held a two-day sy ... Full text Cite

What Can Patient Safety Teach Us About Clinician Burnout?

Journal Article Ann Intern Med · December 17, 2019 Full text Link to item Cite

Creating a Global Roadmap for Healthy Longevity.

Journal Article J Gerontol A Biol Sci Med Sci · November 13, 2019 Full text Link to item Cite

Future of Hypertension.

Journal Article Hypertension · September 2019 Full text Link to item Cite

Induced cardiomyocyte maturation: Cardiac transcription factors are necessary but not sufficient.

Journal Article PLoS One · 2019 The process by which fibroblasts are directly reprogrammed into cardiomyocytes involves two stages; initiation and maturation. Initiation represents the initial expression of factors that induce fibroblasts to transdifferentiate into cardiomyocytes. Follow ... Full text Link to item Cite

Foreword II

Book · January 1, 2019 Cite

Wake-up call from Hong Kong.

Journal Article Science · December 14, 2018 Full text Link to item Cite

Introduction.

Journal Article Semin Oncol Nurs · December 2018 Full text Link to item Cite

Ending Sexual Harassment in Academic Medicine.

Journal Article N Engl J Med · October 25, 2018 Full text Link to item Cite

Health and societal implications of medical and technological advances.

Journal Article Sci Transl Med · October 17, 2018 Scientific and technological breakthroughs are transforming the future of medicine and health, but they inevitably carry risks and have societal implications that need to be addressed proactively. ... Full text Link to item Cite

Insights from molecular signature of in vivo cardiac c-Kit(+) cells following cardiac injury and β-catenin inhibition.

Journal Article J Mol Cell Cardiol · October 2018 There is much interest over resident c-Kit(+) cells in tissue regeneration. Their role in cardiac regeneration has been controversial. In this study we aim to understand the in vivo behavior of cardiac c-Kit(+) cells at baseline and after myocardial infarc ... Full text Link to item Cite

Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B.

Journal Article Stem Cells · August 2018 The process by which committed precursors mature into cardiomyocytes is poorly understood. We found that TLR3 inhibition blocked cardiomyocyte maturation; precursor cells committed to the cardiomyocyte lineage failed to express maturation genes and sarcome ... Full text Link to item Cite

Understanding the mechanism of bias signaling of the insulin-like growth factor 1 receptor: Effects of LL37 and HASF.

Journal Article Cell Signal · June 2018 The development of biased agonist drugs is widely recognized to be important for the treatment of many diseases, including cardiovascular disease. While GPCR biased agonism has been heavily characterized there is a distinct lack of information with respect ... Full text Link to item Cite

The proximity-labeling technique BioID identifies sorting nexin 6 as a member of the insulin-like growth factor 1 (IGF1)-IGF1 receptor pathway.

Journal Article J Biol Chem · April 27, 2018 The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase with critical roles in various biological processes. Recent results from clinical trials targeting IGF1R indicate that IGF1R signaling pathways are more complex than previously ... Full text Link to item Cite

Good gun policy needs research.

Journal Article Science · March 16, 2018 Full text Link to item Cite

Molecular and cellular biology of angiotensin-mediated growth of the cardiovascular system

Chapter · January 1, 2018 Control of vascular smooth muscle cell (VSMC) and myocyte growth is key to the pathophysiology of many vascular diseases such as restenosis, atherosclerosis, and hypertension-induced hypertrophy. This growth control is highly complex and involves the combi ... Full text Cite

The Future Role of the United States in Global Health: Emphasis on Cardiovascular Disease.

Journal Article J Am Coll Cardiol · December 26, 2017 U.S. global health investment has focused on detection, treatment, and eradication of infectious diseases such as tuberculosis, malaria, and human immunodeficiency virus/acquired immunodeficiency syndrome, with significant results. Although efforts should ... Full text Link to item Cite

Commentary: Vaccines-Protecting Health and Saving Lives.

Journal Article Psychol Sci Public Interest · December 2017 Full text Link to item Cite

Creating Healthy Communities after Disasters.

Journal Article N Engl J Med · November 9, 2017 Full text Link to item Cite

Mesenchymal stem cells in obesity: insights for translational applications.

Journal Article Lab Invest · October 2017 Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an ... Full text Link to item Cite

Investing in Global Health for Our Future.

Journal Article N Engl J Med · September 28, 2017 Full text Link to item Cite

Demethylation of H3K27 Is Essential for the Induction of Direct Cardiac Reprogramming by miR Combo.

Journal Article Circ Res · April 28, 2017 RATIONALE: Direct reprogramming of cardiac fibroblasts to cardiomyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo usin ... Full text Link to item Cite

Vital Directions for Health and Health Care: Priorities From a National Academy of Medicine Initiative.

Journal Article JAMA · April 11, 2017 IMPORTANCE: Recent discussion has focused on questions related to the repeal and replacement of portions of the Affordable Care Act (ACA). However, issues central to the future of health and health care in the United States transcend the ACA provisions rec ... Full text Link to item Cite

Debate on the cost of innovation in healthcare: Is it too costly?

Journal Article BMJ Simulation and Technology Enhanced Learning · March 1, 2017 Full text Cite

HASF (C3orf58) is a novel ligand of the insulin-like growth factor 1 receptor.

Journal Article Biochem J · February 20, 2017 We have recently shown that hypoxia and Akt-induced stem cell factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effec ... Full text Link to item Cite

Tissue-engineered 3-dimensional (3D) microenvironment enhances the direct reprogramming of fibroblasts into cardiomyocytes by microRNAs.

Journal Article Sci Rep · December 12, 2016 We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. Reprogramming of cardiac fibroblasts by miR combo in vivo is associated with improved cardiac ... Full text Link to item Cite

Assessment of economic vulnerability to infectious disease crises.

Journal Article Lancet · November 12, 2016 Infectious disease crises have substantial economic impact. Yet mainstream macroeconomic forecasting rarely takes account of the risk of potential pandemics. This oversight contributes to persistent underestimation of infectious disease risk and consequent ... Full text Link to item Cite

Deletion of angiotensin II type 2 receptor accelerates adipogenesis in murine mesenchymal stem cells via Wnt10b/beta-catenin signaling.

Journal Article Lab Invest · August 2016 Recent evidence suggests that the renin-angiotensin system (RAS) has a vital role in adipocyte biology and the pathophysiology of metabolic syndrome. Obesity is the main culprit of metabolic syndrome; and mesenchymal stem cells (MSCs) have been forwarded a ... Full text Link to item Cite

Toward a Common Secure Future: Four Global Commissions in the Wake of Ebola.

Journal Article PLoS Med · May 2016 Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats. ... Full text Link to item Cite

The Institute of Medicine: ensuring integrity and independence in scientific advice on health.

Journal Article Lancet · April 16, 2016 National science and medical academies across the world serve a range of roles and functions. In particular, the benefits of an independent academy tasked with the provision of formal advice are compelling. For nearly half a century, the Institute of Medic ... Full text Link to item Cite

Tracking mesenchymal stromal cells using an ultra-bright TAT-functionalized plasmonic-active nanoplatform.

Journal Article J Biophotonics · April 2016 High-resolution tracking of stem cells remains a challenging task. An ultra-bright contrast agent with extended intracellular retention is suitable for in vivo high-resolution tracking of stem cells following the implantation. Here, a plasmonic-active nano ... Full text Link to item Cite

Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog.

Journal Article Sci Rep · March 15, 2016 We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventua ... Full text Link to item Cite

Nuclear hormone receptor LXRα inhibits adipocyte differentiation of mesenchymal stem cells with Wnt/beta-catenin signaling.

Journal Article Lab Invest · February 2016 Nuclear hormone receptor liver X receptor-alpha (LXRα) has a vital role in cholesterol homeostasis and is reported to have a role in adipose function and obesity although this is controversial. Conversely, mesenchymal stem cells (MSCs) are suggested to be ... Full text Link to item Cite

Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology.

Journal Article Circ Res · January 8, 2016 In the past decade, substantial evidence supports the paradigm that stem cells exert their reparative and regenerative effects, in large part, through the release of biologically active molecules acting in a paracrine fashion on resident cells. The data su ... Full text Link to item Cite

Creating a Global Health Risk Framework.

Journal Article N Engl J Med · September 10, 2015 Full text Link to item Cite

Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways.

Journal Article J Mol Cell Cardiol · August 2015 Wnt signaling has recently emerged as an important regulator of cardiac progenitor cell proliferation and differentiation, but the exact mechanisms by which Wnt signaling modulates these effects are not known. Understanding these mechanisms is essential fo ... Full text Link to item Cite

Blockade of angiotensin II type 2 receptor by PD123319 inhibits osteogenic differentiation of human mesenchymal stem cells via inhibition of extracellular signal-regulated kinase signaling.

Journal Article J Am Soc Hypertens · July 2015 Recent evidence indicates that the vasculature contains mesenchymal stem cells (MSCs). We hypothesized that angiotensin II (Ang II) type 2 receptors (AT2Rs) play a role in the osteogenesis of MSCs and may have a role in vascular calcification. Human MSCs w ... Full text Link to item Cite

Mentorship in Academic Medicine: A Catalyst of Talents.

Journal Article Ann Acad Med Singap · July 2015 Link to item Cite

Global implementation of genomic medicine: We are not alone.

Journal Article Sci Transl Med · June 3, 2015 Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit fr ... Full text Link to item Cite

MicroRNAs and Cardiac Regeneration.

Journal Article Circ Res · May 8, 2015 The human heart has a limited capacity to regenerate lost or damaged cardiomyocytes after cardiac insult. Instead, myocardial injury is characterized by extensive cardiac remodeling by fibroblasts, resulting in the eventual deterioration of cardiac structu ... Full text Link to item Cite

Salt restriction leads to activation of adult renal mesenchymal stromal cell-like cells via prostaglandin E2 and E-prostanoid receptor 4.

Journal Article Hypertension · May 2015 Despite the importance of juxtaglomerular cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchy ... Full text Link to item Cite

The Angiotensin AT2 Receptor: From Enigma to Therapeutic Target

Journal Article · April 22, 2015 Since its discovery, 25 years ago, the angiotensin AT2 receptor (AT2R) has puzzled the scientific community because of its distinct -localization, regulation, signaling pathways, and biological effects separating it clearly from the c ... Full text Cite

The Protective Arm of the Renin Angiotensin System (RAS): Functional Aspects and Therapeutic Implications

Journal Article Protective Arm of the Renin Angiotensin System Ras Functional Aspects and Therapeutic Implications · April 22, 2015 The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early ... Full text Cite

Future Directions

Chapter · April 7, 2015 To continue meeting their missions, academic health centers must make bold transformative changes. They must extensively reform their systems for care delivery and financing, improve the productivity of research, and reduce the cost of medical education. A ... Full text Cite

MicroRNA induced cardiac reprogramming in vivo: evidence for mature cardiac myocytes and improved cardiac function.

Journal Article Circ Res · January 30, 2015 RATIONALE: A major goal for the treatment of heart tissue damaged by cardiac injury is to develop strategies for restoring healthy heart muscle through the regeneration and repair of damaged myocardium. We recently demonstrated that administration of a spe ... Full text Link to item Cite

Role of Paracrine Mechanisms

Chapter · January 1, 2015 Many studies have demonstrated that the exogenous delivery of stem cells into injured myocardium results in functional improvements. It was originally thought that the regenerative properties of these stem cells arose from engraftment into the myocardium a ... Full text Cite

Foreword

Journal Article Law & Contemporary Problems · 2015 Open Access Link to item Cite

Abi3bp regulates cardiac progenitor cell proliferation and differentiation.

Journal Article Circ Res · December 5, 2014 RATIONALE: Cardiac progenitor cells (CPCs) are thought to differentiate into the major cell types of the heart: cardiomyocytes, smooth muscle cells, and endothelial cells. We have recently identified ABI family, member 3 (NESH) binding protein (Abi3bp) as ... Full text Link to item Cite

Straight talk with...Victor Dzau. Interview by Roxanne Khamsi.

Journal Article Nat Med · April 2014 For more than four decades, the US Institute of Medicine (IOM) has operated as an independent nonprofit organization with a mission of providing guiding documents on matters of health and biomedical research, many of which are commissioned by the governmen ... Full text Link to item Cite

HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection.

Journal Article J Mol Cell Cardiol · January 2014 Despite advances in the treatment of acute tissue ischemia significant challenges remain in effective cytoprotection from ischemic cell death. It has been documented that injected stem cells, such as mesenchymal stem cells (MSCs), can confer protection to ... Full text Link to item Cite

Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs.

Journal Article Methods Mol Biol · 2014 The therapeutic administration of microRNAs represents an innovative reprogramming strategy with which to advance cardiac regeneration and personalized medicine. Recently, a distinct set of microRNAs was found capable of converting murine fibroblasts to ca ... Full text Link to item Cite

Fostering innovation in medicine and health care: what must academic health centers do?

Journal Article Acad Med · October 2013 There is a real need for innovation in health care delivery, as well as in medicine, to address related challenges of access, quality, and affordability through new and creative approaches. Health care environments must foster innovation, not just allowing ... Full text Link to item Cite

C3orf58, a novel paracrine protein, stimulates cardiomyocyte cell-cycle progression through the PI3K-AKT-CDK7 pathway.

Journal Article Circ Res · August 2, 2013 RATIONALE: The regenerative capacity of the heart is markedly diminished shortly after birth, coinciding with overall withdrawal of cardiomyocytes from cell cycle. Consequently, the adult mammalian heart has limited capacity to regenerate after injury. The ... Full text Link to item Cite

Abi3bp is a multifunctional autocrine/paracrine factor that regulates mesenchymal stem cell biology.

Journal Article Stem Cells · August 2013 Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over-expressing AKT1 (Akt-MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigate ... Full text Link to item Cite

Adult renal mesenchymal stem cell-like cells contribute to juxtaglomerular cell recruitment.

Journal Article J Am Soc Nephrol · July 2013 The renin-angiotensin-aldosterone system (RAAS) regulates BP and salt-volume homeostasis. Juxtaglomerular (JG) cells synthesize and release renin, which is the first and rate-limiting step in the RAAS. Intense pathologic stresses cause a dramatic increase ... Full text Link to item Cite

Fostering creativity: how the Duke Graduate Medical Education Quasi-Endowment encourages innovation in GME.

Journal Article Acad Med · February 2013 The Duke Medicine Graduate Medical Education Quasi-Endowment, established in 2006, provides infrastructure support and encourages educational innovation. The authors describe Duke's experience with the "grassroots innovation" part of the fund, the Duke Inn ... Full text Link to item Cite

MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes.

Journal Article Circ Res · May 25, 2012 RATIONALE: Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas ... Full text Link to item Cite

Introduction

Journal Article Tropical Forest Conservation and Industry Partnership an Experience from the Congo Basin · March 16, 2012 Full text Cite

Perspective: global medicine: opportunities and challenges for academic health science systems.

Journal Article Acad Med · September 2011 Globalization is having a growing impact on health and health care, presenting challenges as well as opportunities for the U.S. health care industry in general and for academic health science systems (AHSSs) in particular. The authors believe that AHSSs mu ... Full text Link to item Cite

Training the next generation of physician-executives: an innovative residency pathway in management and leadership.

Journal Article Acad Med · May 2011 The rapidly changing field of medicine demands that future physician-leaders excel not only in clinical medicine but also in the management of complex health care enterprises. However, many physicians have become leaders "by accident," and the active culti ... Full text Link to item Cite

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart.

Journal Article J Mol Cell Cardiol · February 2011 Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular ... Full text Link to item Cite

Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction.

Journal Article Proc Natl Acad Sci U S A · December 7, 2010 Secreted frizzled related protein 2 (Sfrp2) is known as an inhibitor for the Wnt signaling. In recent studies, Sfrp2 has been reported to inhibit the activity of Xenopus homolog of mammalian Tolloid-like 1 metalloproteinase. Bone morphogenic protein 1 (Bmp ... Full text Link to item Cite

The Cardiovascular Continuum extended: aging effects on the aorta and microvasculature.

Journal Article Vasc Med · December 2010 The 'Cardiovascular Continuum' was described by Dzau and colleagues in 2006 to explain the development over many years of coronary disease with its complications, then end-stage heart failure. The Continuum identified different points along the way where t ... Full text Link to item Cite

Adult Stem Cell-Based Therapy for the Heart

Journal Article · December 1, 2010 This chapter dicusses the regenerative properties of stem cell as a medicine for heart therapy. The ability to mobilize and activate endogenous stem/progenitor cells in diseased organs or to introduce exogenous stem cells for tissue regeneration/repair may ... Full text Cite

Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

Journal Article Hum Gene Ther · November 2010 The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascula ... Full text Open Access Link to item Cite

Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

Journal Article Circ Res · June 11, 2010 RATIONALE: Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment ... Full text Link to item Cite

Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.

Journal Article J Biol Chem · April 16, 2010 Renin is a key enzyme for cardiovascular and renal homeostasis and is produced by highly specialized endocrine cells in the kidney, known as juxtaglomerular (JG) cells. The nature and origin of these cells remain as mysteries. Previously, we have shown tha ... Full text Link to item Cite

Foreword

Journal Article Air Force Law Review · 2010 Link to item Cite

Adult Stem Cell-Based Therapy for the Heart

Chapter · January 1, 2010 This chapter dicusses the regenerative properties of stem cell as a medicine for heart therapy. The ability to mobilize and activate endogenous stem/progenitor cells in diseased organs or to introduce exogenous stem cells for tissue regeneration/repair may ... Full text Cite

Helmut Drexler, MD, 1951-2009.

Journal Article Circulation · December 8, 2009 Full text Link to item Cite

Nasal vaccination with troponin reduces troponin specific T-cell responses and improves heart function in myocardial ischemia-reperfusion injury.

Journal Article Int Immunol · July 2009 Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood-microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the dam ... Full text Link to item Cite

Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction.

Journal Article Stem Cells · April 2009 Administration of mesenchymal stem cells (MSCs) is an effective therapy to repair cardiac damage after myocardial infarction (MI) in experimental models. However, the mechanisms of action still need to be elucidated. Our group has recently suggested that M ... Full text Link to item Cite

Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a.

Journal Article J Mol Cell Cardiol · March 2009 We have demonstrated that mesenchymal stem cells overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and in vitro through the release of secreted frizzled related protein 2 (Sfrp2). However, the mechanisms ... Full text Link to item Cite

Paracrine mechanisms in adult stem cell signaling and therapy.

Journal Article Circ Res · November 21, 2008 Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. How ... Full text Link to item Cite

Introduction

Journal Article Cardiovascular Genetics and Genomics for the Cardiologist · April 15, 2008 Full text Cite

The Gene in the Twenty-First Century

Journal Article · April 15, 2008 Full text Cite

Improving the health of the community: Duke's experience with community engagement.

Journal Article Acad Med · April 2008 Evidence is accumulating that the United States is falling behind in its potential to translate biomedical advances into practical applications for the population. Societal forces, increased awareness of health disparities, and the direction of clinical an ... Full text Link to item Cite

A global partnership in medical education between Duke University and the National University of Singapore.

Journal Article Acad Med · February 2008 Duke University and the National University of Singapore (NUS) have partnered to launch a new medical school that brings the American style of postbaccalaureate medical education to Asia. The new institution, called the Duke-NUS Graduate Medical School (GM ... Full text Link to item Cite

SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a.

Journal Article Stem Cells · January 2008 Wnts comprise a family of 20 lipid-modified glycoproteins in mammals and play critical roles during embryological development and organogenesis of several organ systems, including the heart. They are required for mesoderm formation and have been implicated ... Full text Link to item Cite

Heme-oxygenase-1-induced protection against hypoxia/reoxygenation is dependent on biliverdin reductase and its interaction with PI3K/Akt pathway.

Journal Article J Mol Cell Cardiol · November 2007 Heme-oxygenase-1 (HO-1), a stress-inducible protein, is an important cytoprotective agent against ischemia/reperfusion (I/R) injury. However, the role of downstream mediators involved in HO-1-induced cytoprotection is not clear. In the current study we inv ... Full text Link to item Cite

Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor 4 for myocardial migration and engraftment.

Journal Article Mol Biol Cell · August 2007 Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this st ... Full text Link to item Cite

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

Journal Article Am J Physiol Heart Circ Physiol · July 2007 We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long ... Full text Link to item Cite

Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.

Journal Article Proc Natl Acad Sci U S A · January 30, 2007 Stem cell therapy has emerged as a promising tool for the treatment of a variety of diseases. Previously, we have shown that Akt-modified mesenchymal stem cells mediate tissue repair through paracrine mechanisms. Using a comprehensive functional genomic st ... Full text Link to item Cite

Molecular mechanism of juxtaglomerular cell hyperplasia: a unifying hypothesis.

Journal Article J Am Soc Hypertens · 2007 Renin is the first enzymatic step of the renin angiotensin cascade and plays an important role in cardiovascular homeostasis. Renin is mainly expressed in and released from specialized juxtaglomerular (JG) cells in kidney. JG cells develop hyperplasia in r ... Full text Link to item Cite

Local renin angiotensin expression regulates human mesenchymal stem cell differentiation to adipocytes.

Journal Article Hypertension · December 2006 Clinical and experimental evidence suggest that the renin-angiotensin system (RAS) plays a role in metabolic syndrome. Adipogenesis is suggested to modulate obesity and obesity-related consequences, such as metabolic syndrome. Although mesenchymal stem cel ... Full text Link to item Cite

Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation.

Journal Article Mol Ther · December 2006 We previously reported that intramyocardial injection of bone marrow-derived mesenchymal stem cells overexpressing Akt (MSC-Akt) efficiently repaired infarcted rat myocardium and improved cardiac function. Controversy still exists over the mechanisms by wh ... Full text Link to item Cite

Vascular medicine

Journal Article Vascular Medicine · December 1, 2006 Comprehensive Clinical Nephrology provides you with all the tools you need to manage all forms of kidney disease. Drs. Jürgen Floege, Richard J. Johnson, John Feehally and a team of international experts have updated this fourth edition to include hot topi ... Cite

Physiological genomics of cardiac disease: quantitative relationships between gene expression and left ventricular hypertrophy.

Journal Article Physiol Genomics · October 3, 2006 The pathogenesis of cardiac left ventricular hypertrophy and failure is poorly defined due to the complexity of the disease phenotype. To gain a better understanding of the relationship between gene expression and left ventricular hypertrophy, we employed ... Full text Link to item Cite

Essential role of ICAM-1/CD18 in mediating EPC recruitment, angiogenesis, and repair to the infarcted myocardium.

Journal Article Circ Res · August 4, 2006 Bone marrow-derived endothelial progenitor cells (EPCs) have the ability to migrate to ischemic organs. However, the signals that mediate trafficking and recruitment of these cells are not well understood. Using a functional genomics strategy, we determine ... Full text Link to item Cite

Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement.

Journal Article FASEB J · April 2006 We previously reported that intramyocardial injection of bone marrow-derived mesenchymal stem cells overexpressing Akt (Akt-MSCs) inhibits ventricular remodeling and restores cardiac function measured 2 wk after myocardial infarction. Here, we report that ... Full text Link to item Cite

Vascular medicine: A companion to Braunwald's heart disease

Book · March 24, 2006 Tap into the latest knowledge and approaches to vascular medicine with the comprehensive, clinically oriented coverage of this new addition to the Braunwald's Heart Disease family. You'll find today's best methods for identifying and treating arterial dise ... Full text Cite

Preface

Journal Article Vascular Medicine A Companion to Braunwald S Heart Disease · March 24, 2006 Full text Cite

Chronic recurrent myocardial ischemic injury is significantly attenuated by pre-emptive adeno-associated virus heme oxygenase-1 gene delivery.

Journal Article J Am Coll Cardiol · February 7, 2006 OBJECTIVES: We assessed the hypothesis that overexpression of the antioxidant enzyme heme oxygenase (HO)-1 may protect against chronic recurrent ischemia/reperfusion injury. BACKGROUND: Multiple and recurring episodes of myocardial ischemia can result in s ... Full text Link to item Cite

Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

Journal Article FASEB J · February 2006 We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarctio ... Full text Link to item Cite

Integration of an academic medical center and a community hospital: The Brigham and Women's/Faulkner Hospital experience

Journal Article Academic Medicine · January 1, 2006 Brigham and Women's Hospital (BWH), a major academic tertiary medical center, and Faulkner Hospital (Faulkner), a nearby community teaching hospital, both in the Boston, Massachusetts area, have established a close affiliation relationship under a common c ... Full text Cite

Gene therapy: role in myocardial protection.

Journal Article Handb Exp Pharmacol · 2006 Heart failure associated with coronary artery disease is a major cause of morbidity and mortality. Recent developments in the understanding of the molecular mechanisms of heart failure have led to the identification of novel therapeutic targets which, comb ... Full text Link to item Cite

Introduction

Chapter · December 1, 2005 Full text Cite

Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution.

Journal Article Circulation · November 22, 2005 BACKGROUND: In the vasculature, the angiotensin type 2 (AT2) receptor (AT2R) exerts antiproliferative, antifibrotic, and proapoptotic effects. Normal adult animals have low AT2R expression; however, vascular injury and exposure to proinflammatory cytokines ... Full text Link to item Cite

Enhancing stem cell therapy through genetic modification.

Journal Article J Am Coll Cardiol · October 4, 2005 Full text Link to item Cite

Searching for transcriptional regulators of Ang II-induced vascular pathology.

Journal Article J Clin Invest · September 2005 Ang II plays a key role in cardiovascular regulation and participates in vascular pathobiology, including inflammation and remodeling. Whether these tissue effects are mediated by direct Ang II actions or indirectly as a result of its influence on hemodyna ... Full text Link to item Cite

Cardiac gene expression profiling provides evidence for cytokinopathy as a molecular mechanism in Chagas' disease cardiomyopathy.

Journal Article Am J Pathol · August 2005 Chronic Chagas' disease cardiomyopathy is a leading cause of congestive heart failure in Latin America, affecting more than 3 million people. Chagas' cardiomyopathy is more aggressive than other cardiomyopathies, but little is known of the molecular mechan ... Full text Link to item Cite

Therapeutic potential of endothelial progenitor cells in cardiovascular diseases.

Journal Article Hypertension · July 2005 Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of i ... Full text Link to item Cite

Liver X receptors alpha and beta regulate renin expression in vivo.

Journal Article J Clin Invest · July 2005 The renin-angiotensin-aldosterone system controls blood pressure and salt-volume homeostasis. Renin, which is the first enzymatic step of the cascade, is critically regulated at the transcriptional level. In the present study, we investigated the role of l ... Full text Link to item Cite

Genetic therapies for cardiovascular diseases.

Journal Article Trends Mol Med · May 2005 Recent advances in understanding the molecular and cellular basis of cardiovascular diseases, together with the availability of tools for genetic manipulation of the cardiovascular system, offer possibilities for new treatments. Gene therapies have demonst ... Full text Link to item Cite

The cardiovascular continuum and renin-angiotensin-aldosterone system blockade.

Journal Article J Hypertens Suppl · April 2005 A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the ke ... Link to item Cite

Identification of calcium-modulating cyclophilin ligand (CAML) as transducer of angiotensin II-mediated nuclear factor of activated T cells (NFAT) activation.

Journal Article J Biol Chem · April 1, 2005 Angiotensin II (Ang II) plays a central role in cardiovascular physiology and disease. Ang II type I receptor (AT1) is thought to mediate most actions of Ang II. A novel AT1 receptor intracellular partner called AT1 receptor-associated protein (ATRAP) was ... Full text Link to item Cite

Integration of an academic medical center and a community hospital: the Brigham and Women's/Faulkner hospital experience.

Journal Article Acad Med · March 2005 Brigham and Women's Hospital (BWH), a major academic tertiary medical center, and Faulkner Hospital (Faulkner), a nearby community teaching hospital, both in the Boston, Massachusetts area, have established a close affiliation relationship under a common c ... Full text Link to item Cite

Bioluminescence resonance energy transfer identify scaffold protein CNK1 interactions in intact cells.

Journal Article FEBS Lett · January 31, 2005 Connector enhancer of KSR (CNK) proteins have been proposed to act as scaffolds in the Ras-MAPK pathway. In this work, using in vivo bioluminescence resonance energy transfer (BRET) assays and in vitro co-immunoprecipitation, we show that hCNK1 interacts w ... Full text Link to item Cite

Molecular genetics and genomics of heart failure.

Journal Article Nat Rev Genet · November 2004 Heart failure is a major disease burden worldwide, and its incidence continues to increase as premature deaths from other cardiovascular conditions decline. Although the overall molecular portrait of this multifactorial disease remains incomplete, molecula ... Full text Link to item Cite

Differential gene expression of blood-derived cell lines in familial combined hyperlipidemia.

Journal Article Arterioscler Thromb Vasc Biol · November 2004 OBJECTIVES: The genetic background of familial combined hyperlipidemia (FCHL) is currently unclear. We propose transcriptional profiling as a complementary tool for its understanding. Two hypotheses were tested: the existence of a disease-specific modifica ... Full text Link to item Cite

Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries.

Journal Article Circulation · October 5, 2004 BACKGROUND: The existence of circulating endothelial progenitor cells (CEPCs) has previously been documented. These cells can be mobilized by cytokines and are recruited to sites of injury, where they may participate in tissue repair. In the present study, ... Full text Link to item Cite

Endothelium-targeted gene and cell-based therapies for cardiovascular disease.

Journal Article Arterioscler Thromb Vasc Biol · October 2004 Most common cardiovascular diseases are accompanied by endothelial dysfunction. Because of its predominant role in the pathogenesis of cardiovascular disease, the vascular endothelium is an attractive therapeutic target. The identification of promoter sequ ... Full text Link to item Cite

Nuclear receptor LXRalpha is involved in cAMP-mediated human renin gene expression.

Journal Article Mol Cell Endocrinol · September 30, 2004 The cAMP-signaling pathway plays a crucial role in the regulation of the renin gene, but the mechanism involved remains poorly understood. We have focused our studies of renin gene regulation on the unique cAMP responsive element (huREN/CNRE, -135 to -107) ... Full text Link to item Cite

An initiative in mentoring to promote residents' and faculty members' careers.

Journal Article Acad Med · September 2004 Internal medicine trainees and faculty recognize the value of effective mentoring to help meet the personal and professional needs of residents. However, the paradigm of the mentor-trainee relationship is seriously threatened by increased clinical, researc ... Full text Link to item Cite

European Heart Journal Supplements: Introduction

Journal Article European Heart Journal Supplement · September 1, 2004 Full text Cite

Gene- and cell-based therapies for cardiovascular diseases: Current status and future directions

Journal Article European Heart Journal Supplement · September 1, 2004 Recent advances in understanding the molecular and cellular basis of cardiovascular diseases, together with the availability of tools for genetic manipulation of the cardiovascular system, offer possibilities for new treatments. Gene therapies have demonst ... Full text Cite

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

Journal Article Proc Natl Acad Sci U S A · August 17, 2004 Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a ... Full text Link to item Cite

Risk factor criteria.

Journal Article Circulation · June 29, 2004 Full text Link to item Cite

Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival.

Journal Article Gene Ther · June 2004 In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene ther ... Full text Link to item Cite

Cell cycle-dependent regulation of smooth muscle cell activation.

Journal Article Arterioscler Thromb Vasc Biol · May 2004 OBJECTIVE: Although numerous diseases involving cellular proliferation are also associated with phenotypic changes, there has been little direct evidence that cell phenotype and the cell's response to external stimuli are modified during passage through di ... Full text Link to item Cite

Gene therapy with an E2F transcription factor decoy inhibits cell cycle progression in rat anti-Thy 1 glomerulonephritis.

Journal Article Int J Mol Med · May 2004 Mesangial cell (MC) proliferation is a central feature of many glomerular diseases. Various growth factors and cytokines are known to trigger MC proliferation both in vitro and in vivo. Regardless of the initial stimulus, proliferation is ultimately depend ... Link to item Cite

Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells.

Journal Article Circulation · April 13, 2004 BACKGROUND: Circulating endothelial progenitor cells (EPCs) have been reported previously. In this study, we examined the hypothesis that overexpression of vasculoprotective gene endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in EPCs ... Full text Link to item Cite

Gene and cell-based therapies for heart disease.

Journal Article FASEB J · April 2004 Heart disease remains the prevalent cause of premature death and accounts for a significant proportion of all hospital admissions. Recent developments in understanding the molecular mechanisms of myocardial disease have led to the identification of new the ... Full text Link to item Cite

Potential for germ line transmission after intramyocardial gene delivery by adeno-associated virus.

Journal Article Biochem Biophys Res Commun · January 16, 2004 Intramyocardial injection of adeno-associated virus (AAV) has been shown to be an effective strategy for cardiac gene delivery. This approach leads to long-term gene expression in the heart, offering the possibility of chronic gene therapy. However, the lo ... Full text Link to item Cite

Risk factor criteria

Journal Article Circulation · 2004 Cite

The angiotensin II type I receptor-associated protein, ATRAP, is a transmembrane protein and a modulator of angiotensin II signaling.

Journal Article Mol Biol Cell · December 2003 Our group identified angiotensin II type 1 (AT1) receptor-associated protein (ATRAP) in a yeast two-hybrid screen for proteins that bind to the carboxyl-terminal cytoplasmic domain of the AT1. In this work, we characterize ATRAP as a transmembrane protein ... Full text Link to item Cite

Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy.

Journal Article Circulation · November 25, 2003 BACKGROUND: Blood-borne endothelial cells originating from adult bone marrow were reported previously. These cells have the properties of an endothelial progenitor cell (EPC) and can be mobilized by cytokines and recruited to sites of neovascularization, w ... Full text Link to item Cite

Current perceptions of cardiovascular gene therapy.

Journal Article Am J Cardiol · November 7, 2003 Due to differences in their knowledge base, scientists, health care professionals, and the general public have varying perceptions of the expectations and risks of using gene therapy for the treatment of cardiovascular disease. Gene therapists are aware of ... Full text Link to item Cite

Evolving revascularization approaches for myocardial ischemia.

Journal Article Am J Cardiol · November 7, 2003 Stable angina pectoris secondary to ischemic heart disease is a common and disabling condition. Medical therapy aims to relieve symptoms, improve exercise capacity, and decrease cardiac events by reducing myocardial oxygen demand or improving coronary bloo ... Full text Link to item Cite

Predicting the future of human gene therapy for cardiovascular diseases: what will the management of coronary artery disease be like in 2005 and 2010?

Journal Article Am J Cardiol · November 7, 2003 Gene therapy is the use of gene delivery as a means to achieve high levels of the therapeutic gene product (ie, "drug" delivery) to treat acquired cardiovascular diseases. Human gene therapy for cardiovascular disease is expected to provide important advan ... Full text Link to item Cite

American Journal of Cardiology: Introduction

Journal Article American Journal of Cardiology · November 7, 2003 Full text Cite

Elucidating the molecular mechanism of cardiac remodeling using a comparative genomic approach.

Journal Article Physiol Genomics · October 17, 2003 It is proposed that analysis of global gene expression would provide an understanding of the molecular mechanisms of cardiac remodeling. However, previous studies have only provided "snapshots" of differential gene expression. Furthermore, the differences ... Full text Link to item Cite

Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness.

Journal Article Circulation · October 14, 2003 BACKGROUND: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is ... Full text Link to item Cite

Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts.

Journal Article Nat Med · September 2003 Transplantation of adult bone marrow-derived mesenchymal stem cells has been proposed as a strategy for cardiac repair following myocardial damage. However, poor cell viability associated with transplantation has limited the reparative capacity of these ce ... Full text Link to item Cite

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

Journal Article Gene Ther · September 2003 The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused u ... Full text Link to item Cite

The future of Physiological Genomics.

Journal Article Physiol Genomics · August 15, 2003 Full text Link to item Cite

Risk assessment in cardiovascular disease: From traditional risk factors to genomics

Journal Article European Heart Journal Supplement · August 1, 2003 In addition to the traditional Framingham risk factors, candidate markers for cardiovascular disease are being proposed and their number continues to grow. High-sensitivity C-reactive protein has been validated as a risk factor for both primary and seconda ... Full text Cite

Chromosomal distribution of the human cardiovascular transcriptome.

Journal Article Genomics · May 2003 On the basis of previous observations in chromosomes 21 and 22, we hypothesize that there is a tissue-specific organization of cardiovascular gene transcripts in the human genome. To examine the distribution of heart-derived transcripts, we assigned a nonr ... Full text Link to item Cite

Identification of a novel set of genes regulated by a unique liver X receptor-alpha -mediated transcription mechanism.

Journal Article J Biol Chem · April 25, 2003 We have reported previously that liver X receptor-alpha (LXRalpha) can mediate a novel cAMP-dependent increase in renin and c-myc gene transcription by binding as a monomer to a unique regulatory element termed the cAMP-negative response element (CNRE). To ... Full text Link to item Cite

A genome scan for hypertension susceptibility loci in populations of Chinese and Japanese origins.

Journal Article Am J Hypertens · February 2003 BACKGROUND: Our understanding of genes that predispose to essential hypertension is poor. METHODS: A genome-wide scan for linkage at approximately 10 cM resolution was done on 1425 sibpairs of Chinese and Japanese origins that were concordant for hypertens ... Full text Link to item Cite

Sex dependence and temporal dependence of the left ventricular genomic response to pressure overload.

Journal Article Physiol Genomics · January 15, 2003 To characterize responses of the left ventricle (LV) to pressure overload at the genomic level, we performed high-density microarray analysis on individual mouse LVs. Male and female mice underwent transverse aortic constriction. At 1 day and 30 wk, the LV ... Full text Link to item Cite

Our new requirement for MIAME standards

Journal Article Physiological Genomics · January 1, 2003 Full text Cite

Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies.

Journal Article J Endocrinol · November 2002 Atherosclerotic cardiovascular disease results from complex interactions among multiple genetic and environmental factors. Thus, it is important to elucidate the influence of each factor on cholesterol metabolism. For this purpose, transgenic/gene-targetin ... Full text Link to item Cite

Molecular approaches for the treatment of atherosclerosis.

Journal Article Cardiol Clin · November 2002 Advances in vascular biology and the study of molecular pathophysiology have enabled the design and initial testing of therapeutic principles for cardiovascular intervention at the level of gene expression. This approach can offer an avenue to greatly impa ... Full text Link to item Cite

Angiotensin II is an active mediator of cardiovascular disease

Journal Article Cardiology Review · October 1, 2002 Cite

Construction of a zebrafish cDNA microarray: gene expression profiling of the zebrafish during development.

Journal Article Biochem Biophys Res Commun · September 6, 2002 Vertebrate embryogenesis is a complex process controlled by a transcriptional hierarchy that coordinates the action of thousands of genes. To identify and analyze the expression patterns of these genes, we constructed a zebrafish cDNA microarray containing ... Full text Link to item Cite

Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure.

Journal Article Physiol Genomics · July 12, 2002 Despite similar clinical endpoints, heart failure resulting from dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) appears to develop through different remodeling and molecular pathways. Current understanding of heart failure has been facil ... Full text Link to item Cite

Clustering and heritability of insulin resistance in Chinese and Japanese hypertensive families: a Stanford-Asian Pacific Program in Hypertension and Insulin Resistance sibling study.

Journal Article Hypertens Res · July 2002 The clustering between hypertension and other metabolic abnormalities related to insulin resistance syndrome (IRS) has been investigated in cross-sectional and prospective studies. Offspring studies have revealed that the clustering characteristics of IRS ... Full text Link to item Cite

Transcription factor decoy.

Journal Article Circ Res · June 28, 2002 Full text Link to item Cite

Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray.

Journal Article Am J Pathol · June 2002 To obtain a genomic portrait of heart failure derived from end-stage dilated cardiomyopathy (DCM), we explored expression analysis using the CardioChip, a nonredundant 10,848-element human cardiovascular-based expressed sequence tag glass slide cDNA microa ... Full text Link to item Cite

Endothelial healing in vein grafts: proliferative burst unimpaired by genetic therapy of neointimal disease.

Journal Article Circulation · April 9, 2002 BACKGROUND: Although inhibition of neointimal hyperplasia by cell cycle gene blockade therapy results in improved endothelial cell function in experimental vein grafts, little is known either about endothelial healing immediately after vein grafting or abo ... Full text Link to item Cite

Pathophysiologic and therapeutic importance of tissue ACE: a consensus report.

Journal Article Cardiovasc Drugs Ther · March 2002 Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contribute to cardiovascular disease through direct pathological tissue effects, including vascular remodeling and inflammation, as well as indirect action on nitri ... Full text Link to item Cite

Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene.

Journal Article Circulation · February 5, 2002 BACKGROUND: Ischemia and oxidative stress are the leading mechanisms for tissue injury. An ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protectio ... Full text Link to item Cite

Physiological genomics: implications in hypertension research.

Journal Article Hypertension · February 2002 In this article we delineate the directions in which the study of physiology will take as it becomes integrated with genomics. We also provide specific examples of the ways in which physiological genomics may be applied to study the complex genetics of hyp ... Full text Link to item Cite

Genetic targeting for cardiovascular therapeutics: Are we near the summit or just beginning the climb?

Journal Article Physiological Genomics · January 1, 2002 This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal ... Cite

Targeted gene therapy for rat glomerulonephritis using HVJ-immunoliposomes.

Journal Article J Gene Med · 2002 BACKGROUND: Kidney targeted gene transfer has been attempted by many researchers over the last 10 years; however, unfortunately, no reliable technique for gene transfer to the kidney has been established. At experimental level several in vivo gene transfer ... Full text Link to item Cite

Physiological Genomics: Who we are and where we're going.

Journal Article Physiol Genomics · December 21, 2001 Full text Link to item Cite

Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb?

Journal Article Physiol Genomics · December 21, 2001 This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal ... Full text Link to item Cite

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Journal Article Am J Cardiol · November 8, 2001 Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal dis ... Full text Link to item Cite

Genetic variation in aldosterone synthase predicts plasma glucose levels.

Journal Article Proc Natl Acad Sci U S A · November 6, 2001 The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels ... Full text Link to item Cite

Cardiovascular genomics: estimating the total number of genes expressed in the human cardiovascular system.

Journal Article J Mol Cell Cardiol · October 2001 The number of genes encoded by the human genome has long sought to be determined. With the recent publications of the complete sequence of the human genome, the number of genes encoded by the human genome has now been estimated to be approximately 32,000-3 ... Full text Link to item Cite

Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice.

Journal Article Circ Res · July 20, 2001 Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiom ... Full text Link to item Cite

Cell cycle protein expression in vascular smooth muscle cells in vitro and in vivo is regulated through phosphatidylinositol 3-kinase and mammalian target of rapamycin.

Journal Article Arterioscler Thromb Vasc Biol · July 2001 Cell cycle progression represents a key event in vascular proliferative diseases, one that depends on an increased rate of protein synthesis. An increase in phosphatidylinositol 3-kinase (PI 3-kinase) activity is associated with vascular smooth muscle cell ... Full text Link to item Cite

High-throughput genotyping with single nucleotide polymorphisms.

Journal Article Genome Res · July 2001 To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination a ... Full text Link to item Cite

Intracellular third loops in AT1 and AT2 receptors determine subtype specificity.

Journal Article Life Sci · June 22, 2001 The recently cloned angiotensin II type 2 (AT2) receptor is a member of the seven transmembrane G-protein coupled receptor superfamily with a relatively low sequence homology with the angiotensin II type 1 (AT1) receptor subtype and counteracts the growth ... Full text Link to item Cite

Genomics and the pathophysiology of heart failure.

Journal Article Curr Cardiol Rep · May 2001 Heart failure is not a single disease entity, but a syndrome with various causes, including hypertension, ischemic and congenital heart disease, cardiomyopathy, and myocarditis. Because of the multiple etiologies and secondary adaptations contributing to h ... Full text Link to item Cite

Long-term stabilization of vein graft wall architecture and prolonged resistance to experimental atherosclerosis after E2F decoy oligonucleotide gene therapy.

Journal Article J Thorac Cardiovasc Surg · April 2001 OBJECTIVE: We tested the hypothesis that a single intraoperative transfection of rabbit vein grafts with a decoy oligonucleotide that blocks cell-cycle gene transactivation by the transcription factor E2F induces long-term stable adaptation that involves m ... Full text Link to item Cite

Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: a unifying hypothesis.

Journal Article Hypertension · April 2001 There is increasing evidence that direct pathobiological events in the vessel wall play an important role in vascular disease. An important mechanism involves the perturbation of the homeostatic balance between NO and reactive oxygen species. Increased rea ... Full text Link to item Cite

Gene therapy for human bypass grafts.

Journal Article Ann Med · April 2001 Autologous saphenous vein is the conduit of choice for the bypass of arterial occlusive disease, be it in the peripheral arterial tree or in the coronary system. This technique is limited by primary graft failure rates approaching 20% in the first year for ... Full text Link to item Cite

New Vistas in Therapeutics: From Drug Design to Gene Therapy: Introduction

Journal Article Annals of the New York Academy of Sciences · January 1, 2001 Full text Cite

Vascular biology: the past 50 years.

Journal Article Circulation · November 14, 2000 Full text Link to item Cite

Molecular mechanism of fibronectin gene activation by cyclic stretch in vascular smooth muscle cells.

Journal Article J Biol Chem · November 3, 2000 Fibronectin plays an important role in vascular remodeling. A functional interaction between mechanical stimuli and locally produced vasoactive agents is suggested to be crucial for vascular remodeling. We examined the effect of mechanical stretch on fibro ... Full text Link to item Cite

Inhibitory effect of angiotensin II type 2 receptor on coronary arterial remodeling after aortic banding in mice.

Journal Article Circulation · October 3, 2000 BACKGROUND: The renin-angiotensin system is thought to be critical for the development of cardiac hypertrophy, whereas the role of the angiotensin II type 2 (AT(2)) receptor in the process is not defined. Using the AT(2) receptor-null (Agtr2-) mouse, we te ... Full text Link to item Cite

Expression of renin-angiotensin system and extracellular matrix genes in cardiovascular cells and its regulation through AT1 receptor.

Journal Article Mol Cell Biochem · September 2000 Angiotensinogen (AGT) is a unique substrate of the renin-angiotensin system and fibronectin (FN) is an important component of the extracellular matrix. These play critical roles in the pathophysiological changes including cardiovascular remodeling and hype ... Link to item Cite

Transcription factor decoy for NFkappaB inhibits TNF-alpha-induced cytokine and adhesion molecule expression in vivo.

Journal Article Gene Ther · August 2000 The expression of several cytokines and adhesion molecules is regulated by the transcription factor NFkappaB, which is activated by tumor necrosis factor alpha (TNF-alpha). In this study, we employed a mouse model of nephritis induced by TNF-alpha to exami ... Full text Link to item Cite

LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression.

Journal Article Proc Natl Acad Sci U S A · July 18, 2000 LXRalpha is a member of a nuclear receptor superfamily that regulates transcription. LXRalpha forms a heterodimer with RXRalpha, another member of this family, to regulate the expression of cholesterol 7alpha-hydroxylase by means of binding to the DR4-type ... Full text Link to item Cite

Systemic administration of HVJ viral coat-liposome complex containing human insulin vector decreases glucose level in diabetic mouse: A model of gene therapy.

Journal Article Biochem Biophys Res Commun · July 5, 2000 In this study, we examined the feasibility of a systemic administration of HVJ-liposome complex containing human insulin construct into the blood in mice via the tail vein. Transfection of human insulin vector resulted in a transient decrease in serum gluc ... Full text Link to item Cite

Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations.

Journal Article Am J Hypertens · June 2000 Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is ... Full text Link to item Cite

Inflammation influences vascular remodeling through AT 2 receptor expression and signaling

Journal Article Physiological Genomics · May 1, 2000 The AT 2 receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model ... Cite

Antisense oligodeoxynucleotide inhibition of vascular angiotensin-converting enzyme expression attenuates neointimal formation: evidence for tissue angiotensin-converting enzyme function.

Journal Article Arterioscler Thromb Vasc Biol · April 2000 It has been proposed that vascular angiotensin-converting enzyme (ACE) plays an important role in regulating vascular growth. Indeed, ACE inhibitors have been reported to prevent neointimal formation after vascular injury in a rat carotid artery model. How ... Full text Link to item Cite

Measuring contributions to the research mission of medical schools.

Journal Article Acad Med · March 2000 The authors of this article, who were the members and staff of a research panel formed by the AAMC as part of its mission-based management initiative, reflect on the growing interest in quantitative information in the management of the research mission of ... Full text Link to item Cite

Inflammation influences vascular remodeling through AT2 receptor expression and signaling.

Journal Article Physiol Genomics · January 24, 2000 The AT(2) receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model ... Full text Link to item Cite

Future opportunities for the treatment of cardiovascular disease

Journal Article British Journal of Cardiology · January 1, 2000 As we enter the new millenium, novel therapeutic strategies for cardiovascular disease are focused on three approaches - changing the biology of vascular disease, intervening in the ischaemic event or modifying the post-ischaemic course. ... Cite

Vascular growth factors as an adjunct to surgical revascularization

Journal Article ACC Current Journal Review · January 1, 2000 Strong theoretical concerns remain regarding the overall benefit of these therapies to prospective patients. The majority of the clinical manifestations of ischemic coronary artery disease are believed to result from the obstruction of medium-sized conduit ... Full text Cite

The renin-angiotensin-aldosterone system: a specific target for hypertension management.

Journal Article Am J Hypertens · December 1999 Angiotensin II plays a central role in the regulation of systemic arterial pressure through its systemic synthesis via the renin-angiotensin-aldosterone cascade. It acts directly on vascular smooth muscle as a potent vasoconstrictor. In addition, it affect ... Full text Link to item Cite

Constants and scientific progress.

Journal Article Physiol Genomics · November 11, 1999 Full text Link to item Cite

Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre, randomised, controlled trial.

Journal Article Lancet · October 30, 1999 BACKGROUND: Cell-cycle blockade by ex-vivo gene therapy of experimental vein grafts inhibits the neointimal hyperplasia and subsequent accelerated atherosclerosis that lead to human bypass-graft failure. In a prospective, randomised, controlled trial, we i ... Full text Link to item Cite

Antisense oligodeoxynucleotides prevent acute cardiac allograft rejection via a novel, nontoxic, highly efficient transfection method.

Journal Article Transplantation · September 27, 1999 BACKGROUND: We hypothesized that ex vivo donor allograft transfection with antisense oligodeoxynucleotide (AS ODN) would inhibit the expression of intercellular adhesion molecule (ICAM)-1, an important mediator of T-cell adhesion and costimulation, and the ... Full text Link to item Cite

A pressure-mediated nonviral method for efficient arterial gene and oligonucleotide transfer.

Journal Article Hum Gene Ther · September 20, 1999 In this study, we report a method of controlled pressure-mediated delivery of "naked" DNA that achieves efficient and safe arterial gene and oligonucleotide transfer. We demonstrated a pressure-dependent uptake of fluorescein-labeled (FITC) oligonucleotide ... Full text Link to item Cite

A novel role for the cyclin-dependent kinase inhibitor p27(Kip1) in angiotensin II-stimulated vascular smooth muscle cell hypertrophy.

Journal Article J Clin Invest · September 1999 Angiotensin II (Ang II) has been shown to stimulate either hypertrophy or hyperplasia. We postulated that the differential response of vascular smooth muscle cells (VSMCs) to Ang II is mediated by the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1), whic ... Full text Link to item Cite

Increased vasoconstrictor response of the mouse lacking angiotensin II type 2 receptor.

Journal Article Biochem Biophys Res Commun · August 2, 1999 The angiotensin II (Ang II) type 1 receptor mediates various actions of Ang II, whereas the function of the type 2 (AT2) receptor is not well understood. In the mice lacking the gene encoding the AT2 receptor, the pressor response to Ang II was increased a ... Full text Link to item Cite

Revolution and renaissance.

Journal Article Physiol Genomics · July 15, 1999 Full text Link to item Cite

Analysis of functional domains of angiotensin II type 2 receptor involved in apoptosis.

Journal Article Mol Endocrinol · July 1999 We previously demonstrated that the intracellular third loop (i3 loop) of angiotensin II type 2 receptor (AT2) plays a key role in mediating the biological functions of this receptor. To determine which residues are important for AT2 signaling, mutated rec ... Full text Link to item Cite

Activation of the de novo biosynthesis of sphingolipids mediates angiotensin II type 2 receptor-induced apoptosis.

Journal Article J Biol Chem · June 11, 1999 This study examines the role of sphingolipids in mediating the apoptosis of PC12W cells induced by the angiotensin II type 2 (AT2) receptor. PC12W cells express abundant AT2 receptor but not angiotensin II type 1 receptor and undergo apoptosis when stimula ... Full text Link to item Cite

Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.

Journal Article J Biol Chem · June 11, 1999 The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology. Employing yeast two-hybrid scr ... Full text Link to item Cite

AT2 receptor and vascular smooth muscle cell differentiation in vascular development.

Journal Article Hypertension · June 1999 The angiotensin II type 2 (AT2) receptor is transiently expressed at late gestation in the fetal vasculature, but its expression rapidly declines after birth. We have previously demonstrated that the expression of this receptor mediates decline in vascular ... Full text Link to item Cite

Pressure-mediated oligonucleotide transfection of rat and human cardiovascular tissues.

Journal Article Proc Natl Acad Sci U S A · May 25, 1999 The application of gene therapy to human disease is currently restricted by the relatively low efficiency and potential hazards of methods of oligonucleotide or gene delivery. Antisense or transcription factor decoy oligonucleotides have been shown to be e ... Full text Link to item Cite

Transcription factor decoy to study the molecular mechanism of negative regulation of renin gene expression in the liver in vivo.

Journal Article Circ Res · May 14, 1999 Renin is synthesized in high quantities in the juxtaglomerular cells of the kidney, but little or none is synthesized in the liver. Our previous in vitro and biochemical studies have demonstrated that tissue-specific expression of the mouse renin gene is r ... Full text Link to item Cite

Stimulation of different subtypes of angiotensin II receptors, AT1 and AT2 receptors, regulates STAT activation by negative crosstalk.

Journal Article Circ Res · April 30, 1999 Angiotensin II type 2 (AT2) receptor exerts an inhibitory action on cell growth. In the present study, we report that the stimulation of AT2 receptor in AT2 receptor cDNA-transfected rat adult vascular smooth muscle cells (VSMCs) inhibited angiotensin II t ... Full text Link to item Cite

Recent progress in angiotensin II type 2 receptor research in the cardiovascular system.

Journal Article Hypertension · February 1999 Angiotensin II (Ang II) plays an important role in regulating cardiovascular hemodynamics and structure. Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, and at least 2 distinct receptor subtypes have been defined on the ... Full text Link to item Cite

Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak, and Bcl-x.

Journal Article Circ Res · January 8, 1999 -Cytokine-induced NO production depresses myocardial contractility and has been shown to be cytotoxic to cardiac myocytes. However, the mechanisms of cytokine-induced cardiac myocyte cell death are unclear. To analyze these mechanisms in detail, we treated ... Full text Link to item Cite

AT2 receptor and vascular smooth muscle cell differentiation in vascular development

Journal Article Hypertension · 1999 The angiotensin II type 2 (AT2) receptor is transiently expressed at late gestation in the fetal vasculature, but its expression rapidly declines after birth. We have previously demonstrated that the expression of this receptor mediates decline in vascular ... Cite

Interferon regulatory factors regulate interleukin-1beta-converting enzyme expression and apoptosis in vascular smooth muscle cells.

Journal Article Hypertension · January 1999 -Apoptosis has been reported to play a pivotal role in vascular remodeling. However, cellular mechanisms of apoptosis in vascular smooth muscle cells (VSMCs) have not been well defined. In this study, we focused on interleukin-1beta-converting enzyme (ICE) ... Full text Link to item Cite

Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth.

Journal Article J Clin Invest · January 1999 Angiotensin II type 2 (AT2) receptor is abundantly expressed in vascular smooth muscle cells (VSMC) of the fetal vasculature during late gestation (embryonic day 15-20), during which the blood vessels undergo remodeling. To examine directly the influence o ... Full text Link to item Cite

Genomics and hypertension: concepts, potentials, and opportunities.

Journal Article Hypertension · January 1999 We are at the beginning of a biological revolution, spurred on by the Human Genome Project and associated studies. Within the next few years, expressed sequence tags (ESTs) representing all sequences expressed in humans will be determined and their genomic ... Full text Link to item Cite

Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization.

Journal Article J Thorac Cardiovasc Surg · November 1998 INTRODUCTION: Transmyocardial laser revascularization is believed to induce an angiogenic response within ischemic myocardium. We evaluated transgene expression in the setting of transmyocardial laser revascularization and hypothesized that intramyocardial ... Full text Link to item Cite

Mechanism of protective effects of ACE inhibition on coronary artery disease.

Journal Article Eur Heart J · September 1998 Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular oxidative stress, vascular growth and inflammation, and may directly influence the pathophysiology of coronary artery disease (CAD). The presence of angiotensin-converting enz ... Link to item Cite

An oligonucleotide decoy for transcription factor E2F inhibits mesangial cell proliferation in vitro.

Journal Article Am J Physiol · August 1998 The transcription factor E2F controls expression of several genes involved in cell proliferation including c-myc, c-myb, proliferating cell nuclear antigen (PCNA), and cdk2 kinase. Having established that both PCNA and cdk2 kinase are induced in rat mesang ... Full text Link to item Cite

Cell cycle progression: new therapeutic target for vascular proliferative disease.

Journal Article Circulation · July 7, 1998 Entry into and progression of vascular cells through the cell cycle is considered a key event in vascular proliferative diseases. Multiple growth factors and cytokines have been found to regulate vascular cell proliferation. However, the machinery regulati ... Full text Link to item Cite

Prevention of ischemically induced neointimal hyperplasia using ex vivo antisense oligodeoxynucleotides.

Journal Article J Heart Lung Transplant · April 1998 BACKGROUND: Chronic graft vascular disease in cardiac allografts results from coronary artery neointimal formation. Vascular ischemia has been shown to provoke the development of neointimal hyperplasia through endothelial damage. We used a rodent model of ... Link to item Cite

Role of AP-1 complex in angiotensin II-mediated transforming growth factor-beta expression and growth of smooth muscle cells: using decoy approach against AP-1 binding site.

Journal Article Biochem Biophys Res Commun · February 13, 1998 The cis element double-stranded oligodeoxynucleotides (ODN) ("decoy") approach has enabled us to clarify the responsible elements. Using this approach, we transfected AP-1 decoy ODN into VSMC cultured from WKY rats (WKY Adu) which produce latent TGF-beta, ... Full text Link to item Cite

Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects.

Journal Article J Clin Invest · February 1, 1998 Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, AT1 antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment with AT1 antagonists causes elevation of plasma Ang II which selectively binds ... Full text Link to item Cite

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagonizes angiotensin II type 1 receptor action: an in vitro gene transfer study.

Journal Article Life Sci · 1998 Angiotensin II type 2 (AT2) receptor is expressed abundantly in the fetal vasculature with rapid decline after birth and re-expressed in the adult vasculature after injury, whereas angiotensin II type 1 (AT1) receptor is expressed. We studied their effects ... Full text Link to item Cite

Molecular and cellular mechanism of angiotensin II-mediated apoptosis.

Journal Article Endocr Res · 1998 It is well known that angiotensin II exerts growth promoting effects via the angiotensin II type 1 (AT1) receptor. We have cloned a second type of angiotensin II receptor (AT2 receptor) and demonstrated that this receptor acts as an antagonistic receptor a ... Full text Link to item Cite

Angiotensin II-regulated apoptosis in the cardiovascular system

Journal Article Heart Failure Reviews · January 1, 1998 Full text Cite

How will molecular therapeutics impact cardiovascular diseases?

Journal Article British Journal of Cardiology · January 1, 1998 Cite

Presentation of the 1998 Kober Medal to Eugene Braunwald.

Journal Article Proc Assoc Am Physicians · 1998 Link to item Cite

The comprehensive total genome scan to map genes responsible for high blood pressure in the rat

Journal Article FASEB Journal · December 1, 1997 Using the total genome scan strategy with the rat animal model, the regions of the genome containing quantitative trait loci (QTLs) responsible for more than 300 phenotypes have been identified. We (more than 100 people from 14 institutions) have studied s ... Cite

Loss of p27Kip1 and induction of Cdk1 in the rat carotid artery following ballon catheter injury. in vivo and in vitro influence of rapamycin

Journal Article FASEB Journal · December 1, 1997 Vascular smooth muscle cell proliferation (VSMC) is induced in vitro by serum stimulation or in vivo by balloon catheter injury. We hypothesized that a proliferative response involves changes in the expression of the cyclin-dependent kinase Cdk1 and the Cd ... Cite

Concluding remarks

Journal Article Journal of Hypertension Supplement · December 1, 1997 Cite

Future horizons in cardiovascular molecular therapeutics.

Journal Article Am J Cardiol · November 6, 1997 In the past 2 decades, significant progress has been made in cardiovascular therapeutics. Effective drug therapies have been developed for hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, and congestive heart failure. Nov ... Full text Link to item Cite

Genetic manipulation of vein grafts.

Journal Article Curr Opin Cardiol · November 1997 A greater understanding of the molecular and genetic bases of cardiovascular diseases has made the design of therapeutic genetic interventions feasible in these clinical entities. Bypass vein graft failure represents a serious limitation in the long-term t ... Full text Link to item Cite

Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand.

Journal Article Mol Endocrinol · August 1997 Angiotensin II (Ang II) binds to two different receptor subtypes, AT1 and AT2 receptors. In many cases, receptor stimulation by Ang II is followed by a rapid desensitization of the intracellular signal transduction and a decrease in cell surface receptor n ... Full text Link to item Cite

Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis.

Journal Article J Biol Chem · July 25, 1997 We examined the cellular and signaling mechanism of angiotensin II (Ang II) type 2 (AT2) receptor-induced apoptosis in PC12W (rat pheochromocytoma cell line) cells that express abundant AT2 receptor but not Ang II type 1 receptor. In these cells, nerve gro ... Full text Link to item Cite

Molecular Delivery System for Antisense Oligonucleotides: Enhanced Effectiveness of Antisense Oligonucleotides by HVJ-liposome Mediated Transfer.

Journal Article J Cardiovasc Pharmacol Ther · July 1997 BACKGROUND: The effectiveness of antisense oligodeoxynucleotides for in vitro and in vivo studies is limited by a low efficiency of cellular uptake and instability due to degradation by nucleases. To overcome some of these problems, we recently developed a ... Full text Link to item Cite

DNA transfer into vascular smooth muscle using fusigenic Sendai virus (HVJ)-liposomes.

Journal Article Mol Cell Biochem · July 1997 Manipulation of the genetic machinery of cells both in vitro and in vivo is becoming an ever more important means of elucidating pathways of molecular and cellular biochemistry. In addition, gene therapy has been proposed as a novel and potentially powerfu ... Link to item Cite

Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block.

Journal Article Proc Natl Acad Sci U S A · June 10, 1997 Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the cardiac effects are due to direct actions of Ang II on the myocardium or if they are due to ... Full text Link to item Cite

Interferon regulatory factor-1 up-regulates angiotensin II type 2 receptor and induces apoptosis.

Journal Article J Biol Chem · May 2, 1997 The expression of the angiotensin II type 2 (AT2) receptor is developmentally and growth regulated. In cultured R3T3 cells, expression of this receptor is markedly induced at the confluent state and with serum deprivation. In this study we demonstrated tha ... Full text Link to item Cite

Prevention of restenosis by gene therapy.

Journal Article Ann N Y Acad Sci · April 15, 1997 We have developed an efficient vector system based on the liposome for the delivery of oligonucleotides and genes into various organs. The liposome was decorated with fusion proteins of HVJ (Sendai virus) to introduce DNA directly into the cytoplasm and co ... Full text Link to item Cite

Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome.

Journal Article Mol Cell Endocrinol · March 28, 1997 Angiotensin II type 2 (AT(2)) receptor is highly expressed in the fetal tissues and decreases rapidly after birth. AT(2) receptor is re-expressed in the adult atretic ovarian follicles. Recently, it has been reported that AT(2) receptor mediates apoptosis. ... Full text Link to item Cite

Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts.

Journal Article J Clin Invest · March 15, 1997 We have recently shown that ex vivo gene therapy of rabbit autologous vein grafts with antisense oligodeoxynucleotides (AS ODN) blocking cell cycle regulatory gene expression inhibits not only neointimal hyperplasia, but also diet-induced, accelerated graf ... Full text Link to item Cite

Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)--liposome method.

Journal Article J Mol Cell Cardiol · March 1997 The lack of efficient treatment for myocardial infarction remains an unresolved problem in the field of cardiovascular disease. Gene therapy may be a potential therapeutic strategy for the treatment of myocardial infarction. However, current methods of in ... Full text Link to item Cite

Introduction

Journal Article American Journal of Cardiology · January 1, 1997 Full text Cite

Nitric oxide synthase: role in the genesis of vascular disease.

Journal Article Annu Rev Med · 1997 The product of nitric oxide (NO) synthase is the most potent endogenous vasodilator known. No not only is a potent vasodilator, it also inhibits platelet adherence and aggregation, reduces adherence of leukocytes to the endothelium, and suppresses prolifer ... Full text Link to item Cite

New approaches to cardiovascular therapy: Panel discussion

Journal Article American Journal of Cardiology · January 1, 1997 Full text Cite

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Journal Article J Clin Endocrinol Metab · December 1996 Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role ... Full text Link to item Cite

Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease.

Journal Article Circulation · December 1, 1996 BACKGROUND: Angiotensin may play a pathophysiological role in experimental and human cardiovascular disease. Clinical studies have shown that ACE inhibitors reduce mortality, recurrent myocardial infarction, and ischemic events in patients with left ventri ... Full text Link to item Cite

In vivo gene transfer and gene modulation in hypertension research.

Journal Article Hypertension · December 1996 Transgenic technologies and homologous recombination approaches have been useful for studying the roles of specific genes in systemic hypertension. Recently, we and others have introduced the use of in vivo gene transfer to study the effects of local gene ... Full text Link to item Cite

Fusigenic viral liposome for gene therapy in cardiovascular diseases.

Journal Article Proc Natl Acad Sci U S A · October 15, 1996 To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) ... Full text Link to item Cite

Intracellular third loop domain of angiotensin II type-2 receptor. Role in mediating signal transduction and cellular function.

Journal Article J Biol Chem · September 6, 1996 The present study tests the hypothesis that the unique intracellular third loop domain of angiotensin II type-2 (AT2) receptor is essential for the subsequent intracellular signaling and plays an important role in mediating receptor function. Synthetic int ... Full text Link to item Cite

Gene inhibition and gene augmentation for the treatment of vascular proliferative disorders.

Journal Article Semin Interv Cardiol · September 1996 Gene therapy is emerging as a potential strategy for the treatment of vasculoproliferative diseases such as restenosis after angioplasty, vascular bypass graft occlusion and transplant coronary vasculopathy for which no known effective therapy exists. Our ... Link to item Cite

Fusigenic liposome-mediated DNA transfer into cardiac myocytes.

Journal Article J Mol Cell Cardiol · July 1996 Current methods of gene transfer into cultured cardiac myocytes have serious limitations, including low efficiency, toxicity or constraints on DNA insert size. The present study examined the effectiveness of hemagglutinating virus of Japan (HVJ) in promoti ... Full text Link to item Cite

Molecular therapies for vascular diseases.

Journal Article Science · May 3, 1996 Vascular disease is the most common cause of death in the industrialized world. Although significant progress has been made in treating these disorders, more therapeutic agents must be developed that effectively prevent, arrest, or reverse this disease. Re ... Full text Link to item Cite

Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22.

Journal Article J Clin Invest · May 1, 1996 Resistance to insulin-mediated glucose disposal is a common finding in patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as in nondiabetic individuals with hypertension. In an effort to identify the generic loci responsible for variati ... Full text Link to item Cite

Angiotensin II type 2 receptor mediates programmed cell death.

Journal Article Proc Natl Acad Sci U S A · January 9, 1996 The function of the recently discovered angiotensin II type 2 (AT2) receptor remains elusive. This receptor is expressed abundantly in fetus, but scantily in adult tissues except brain, adrenal medulla, and atretic ovary. In this study, we demonstrated tha ... Full text Link to item Cite

Potential gene therapy using e2f decoy approach with hvj-liposome method to glomerulonephritis in rats

Journal Article Journal of Investigative Medicine · January 1, 1996 Mesangial cell (MC) proliferation is a central feature of the various renal diseases. The process of MC proliferation is dependent on the coordinated activation of a series of cell cycle regulatory genes. The transcriptional factor E2F plays an important r ... Cite

Potential gene therapy for glomerulonephritis: Transfection of NFKB decoy inhibited TNF-A induced cytokine and adhesion molecules expression in vivo

Journal Article Journal of Investigative Medicine · January 1, 1996 Recent studies have demonstrated that numerous cytokines and adhesion molecules are expressed in lesions of experimental and human glomerulonephritis and have speculated their pathophysiological contributions. These genes are regulated by the transcription ... Cite

The guide to cardiology: Heart failure

Journal Article Prevention and Management of Congestive Heart Failure · January 1, 1996 Heart failure is a very common condition that will be encountered across all ages and by family practitioners, internists, and specialists. Patients are frequently aware of the poor prognosis of this condition and will need a high level of support and moni ... Cite

Cloning, characterization, and genetic mapping of the rat type 2 angiotensin II receptor gene.

Journal Article Hypertension · December 1995 The renin-angiotensin system plays an important role in blood pressure homeostasis, but the contribution of the type 2 angiotensin II receptor (AT2R) is still unclear. The reports that the AT2R gene has been mapped to the X chromosome in human and rat and ... Full text Link to item Cite

Linkage mapping of the angiotensin AT2 receptor gene (Agtr2) to the mouse X chromosome.

Journal Article Genomics · November 20, 1995 Angiotensin II is a potent regulator of cardiovascular homeostasis and binds to two different G-protein-coupled receptors. While the type 1 receptor (AT1) mediates the cardiovascular actions of angiotensin II, the function of the recently cloned type 2 rec ... Full text Link to item Cite

The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer.

Journal Article Proc Natl Acad Sci U S A · November 7, 1995 The type 1 angiotensin II (AT1) receptor is well characterized but the type 2 (AT2) receptor remains an enigma. We tested the hypothesis that the AT2 receptor can modulate the growth of vascular smooth muscle cells by transfecting an AT2 receptor expressio ... Full text Link to item Cite

Balloon catheterization induced arterial expression of embryonic fibronectins.

Journal Article Arterioscler Thromb Vasc Biol · November 1995 Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expr ... Full text Link to item Cite

Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice.

Journal Article Nature · October 26, 1995 Angiotensin II, a potent regulator of blood pressure and of water and electrolyte balance, binds to two different G-protein-coupled receptors. The type-1 receptor (AT1) mediates the vasopressive and aldosterone-secreting effects of angiotensin II, but the ... Full text Link to item Cite

[Experimental approaches for gene therapy modification of vascular remodeling].

Journal Article Z Kardiol · October 1995 The active process of vascular remodeling involves changes in several cellular processes like cell growth, cell death, cell migration, and extracellular matrix production or degradation. The recent development of in vivo gene transfer technology has create ... Link to item Cite

Investigation of the phenylethanolamine N-methyltransferase gene as a candidate gene for hypertension.

Journal Article Hypertension · October 1995 Genetic mapping studies have located a gene, Bp1, that accounts for approximately 30% of the genetic variation in the stroke-prone spontaneously hypertensive rat (SHRSP) to a region on chromosome 10 containing the angiotensin-converting enzyme gene. In hum ... Full text Link to item Cite

In vivo identification of a negative regulatory element in the mouse renin gene using direct gene transfer.

Journal Article J Clin Invest · September 1995 DBA/2J mouse contains two renin gene loci (Ren1d and Ren2d). Ren2d but not Ren1d is expressed in submandibular gland (SMG) while both are expressed in the kidney. Based on vitro studies, we have postulated that a negative regulatory element (NRE) in the re ... Full text Link to item Cite

A biometrical genome search in rats reveals the multigenic basis of blood pressure variation.

Journal Article Genome Res · September 1995 A genome-wide search for multiple loci influencing salt-loaded systolic blood pressure (NaSBP) variation among 188 F2 progeny from a cross between the Brown-Norway and spontaneously hypertensive rat strains was pursued in an effort to gain insight into the ... Full text Link to item Cite

A cone-plate apparatus for the in vitro biochemical and molecular analysis of the effect of shear stress on adherent cells

Journal Article Methods in Cell Science · September 1, 1995 Living cells are constantly exposed to a variety of complex mechanical stimuli which are though to be critical in the control of tissue structure and function. Endothelial and smooth muscle cells in the blood vessel are ideal candidates for the study of bl ... Full text Cite

The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2.

Journal Article J Biol Chem · August 25, 1995 Angiotensin II type 2 (AT2) receptor is abundantly and widely expressed in fetal tissues but present only in restricted tissues in the adult such as brain and atretic ovary. This receptor is speculated to be involved in tissue growth and/or differentiation ... Full text Link to item Cite

Molecular biology of angiotensin II biosynthesis and receptors.

Journal Article Can J Cardiol · August 1995 In vitro data suggest that there are complex pathways of angiotensin production and that multiple receptor subtypes mediate the actions of this peptide. These observations may have important in vivo physiological and pharmacological implications. This pape ... Link to item Cite

Characterization of a rat type 2 angiotensin II receptor stably expressed in 293 cells.

Journal Article Mol Cell Endocrinol · July 1995 A cDNA clone for the rat type 2 (AT2) angiotensin II receptor was stably transfected into human embryonic kidney 293 cells. Binding characteristics of CGP42112A (Kd = 0.18 nM, Bmax = 10.8 pmol/mg protein) and ligand specificity were indistinguishable from ... Full text Link to item Cite

Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease.

Journal Article Lancet · June 24, 1995 Several genes, including some encoding components of the renin angiotensin system, are associated with the risk of cardiovascular diseases. There have been reports linking a homozygous deletion allele of the angiotensin converting enzyme (ACE) gene (DD) wi ... Full text Link to item Cite

A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo.

Journal Article Proc Natl Acad Sci U S A · June 20, 1995 The application of DNA technology to regulate the transcription of disease-related genes in vivo has important therapeutic potentials. The transcription factor E2F plays a pivotal role in the coordinated transactivation of cell cycle-regulatory genes such ... Full text Link to item Cite

Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia.

Journal Article Arterioscler Thromb Vasc Biol · June 1995 Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for ... Full text Link to item Cite

Genetic engineering of vein grafts resistant to atherosclerosis.

Journal Article Proc Natl Acad Sci U S A · May 9, 1995 Previously, researchers have speculated that genetic engineering can improve the long-term function of vascular grafts which are prone to atherosclerosis and occlusion. In this study, we demonstrated that an intraoperative gene therapy approach using antis ... Full text Link to item Cite

Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement.

Journal Article Transplantation · March 15, 1995 Rapamycin (RPM) and mycophenolic acid (MPA) inhibit immune responses by antagonizing IL-stimulated lymphocyte activation. These 2 drugs, used alone or preferably in combination, also significantly reduced the response of vascular cells to balloon-catheter ... Full text Link to item Cite

Fluid shear stress induces endothelial transforming growth factor beta-1 transcription and production. Modulation by potassium channel blockade.

Journal Article J Clin Invest · March 1995 The endothelium has the capacity to modulate vascular structure in response to hemodynamic stimuli. We tested the hypothesis that exposure of the endothelium to increased laminar shear stress induces the expression of TGF beta 1 via a signal transduction p ... Full text Link to item Cite

Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.

Journal Article Proc Natl Acad Sci U S A · February 14, 1995 It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular dis ... Full text Link to item Cite

Genetic models of human vascular disease.

Journal Article Circulation · January 15, 1995 The use of genetic models has greatly assisted investigations of the natural history, mechanisms, and potential therapy for human vascular disease. In the past, genetic models of vascular disease were obtained through serendipity and/or selective breeding ... Full text Link to item Cite

A genetic linkage map of the laboratory rat, Rattus norvegicus.

Journal Article Nat Genet · January 1995 We report the construction of the first complete genetic linkage map of the laboratory rat. By testing 1171 simple sequence length polymorphisms (SSLPs), we have identified 432 markers that show polymorphisms between the SHR and BN rat strains and mapped t ... Full text Link to item Cite

Angiotensin converting enzyme as a multimechanistic factor in CAD

Journal Article Journal of Myocardial Ischemia · January 1, 1995 Recent advances in cardiovascular research have improved our understanding of the continuum of events leading to end-stage coronary artery disease (CAD). Therapeutic agents have also been introduced that intervene at various stages of CAD development. Angi ... Cite

Desensitization of angiotensin receptor function.

Journal Article Kidney Int · December 1994 Angiotensin II is an eight amino acid peptide which plays a major role in the regulation of cardiovascular homeostasis. The physiologic effects of angiotensin (Ang) II are mediated by a G-protein coupled receptor, termed AT1, which activates phospholipase ... Full text Link to item Cite

Pathobiology of atherosclerosis and plaque complications.

Journal Article Am Heart J · December 1994 To understand the process of atherosclerosis, the homeostatic and protective functions of the endothelium must be considered. The endothelium serves as the interface between blood flow and the vascular tissues. It normally regulates vascular tone and struc ... Full text Link to item Cite

Pharmacokinetics of antisense oligodeoxyribonucleotides (cyclin B1 and CDC 2 kinase) in the vessel wall in vivo: enhanced therapeutic utility for restenosis by HVJ-liposome delivery.

Journal Article Gene · November 4, 1994 Using a highly efficient viral HVJ (hemagglutinating virus of Japan) liposome-mediated transfer method, we examined the cellular fate of antisense oligodeoxyribonucleotides (oligos) in the vessel wall in vivo. Direct transfer of unmodified FITC (fluorescei ... Full text Link to item Cite

Human type 2 angiotensin II receptor gene: cloned, mapped to the X chromosome, and its mRNA is expressed in the human lung.

Journal Article Biochem Biophys Res Commun · September 30, 1994 The human type 2 angiotensin II receptor (AT2R) gene was isolated from a human genomic DNA library of adult female leukocytes. The putative coding region of the human AT2R gene is intronless. The primary structure of the human AT2R deduced from the nucleot ... Full text Link to item Cite

The vasculopathy of aging.

Journal Article J Gerontol · September 1994 Full text Link to item Cite

Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme.

Journal Article J Clin Invest · September 1994 In vitro studies have demonstrated that angiotensin (Ang) II directly stimulates vascular smooth muscle cell (VSMC) growth. However, it is still unclear if Ang II exerts a direct effect on vascular hypertrophy in vivo independent of its effect on blood pre ... Full text Link to item Cite

Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothelial cellular growth.

Journal Article J Clin Invest · August 1994 In addition to the atria, recent evidence suggests that atrial natriuretic peptide (ANP) is also synthesized in other tissues. Of particular interest is the location of ANP mRNA in the vessel wall. We and others have shown that exogenously added ANP inhibi ... Full text Link to item Cite

Potential importance of tissue angiotensin-converting enzyme inhibition in preventing neointima formation.

Journal Article Circulation · July 1994 BACKGROUND: Angiotensin II (Ang II) induces vascular smooth muscle cell migration and growth in vitro and induces DNA synthesis in vascular smooth muscle in vivo. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists inhibi ... Full text Link to item Cite

Molecular biology of angiotensin receptors: target for drug research?

Journal Article J Hypertens Suppl · July 1994 UNLABELLED: Angiotensin II receptors: Angiotensin II is a key regulator of cardiovascular homeostasis. At least two distinct angiotensin II receptor subtypes are defined, on the basis of their differential pharmacological and biochemical properties, and de ... Link to item Cite

Cell biology and genetics of angiotensin in cardiovascular disease.

Journal Article J Hypertens Suppl · July 1994 GROWTH-PROMOTING EFFECTS OF ANGIOTENSIN: Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular and cardiac growth and may directly influence the pathophysiology of coronary artery disease and ventricular remodeling. Vascular grow ... Link to item Cite

New perspectives in hypertension research. Potentials of vascular biology.

Journal Article Hypertension · June 1994 The vessel wall was once considered to be a passive conduit responding to the circulating endocrine system. However, the emergence of molecular and vascular biology in hypertension research has redefined our understanding of the role of the vasculature as ... Full text Link to item Cite

The emerging concept of vascular remodeling.

Journal Article N Engl J Med · May 19, 1994 Full text Link to item Cite

Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides.

Journal Article J Clin Invest · April 1994 The cell cycle regulatory enzyme, cdk (cyclin-dependent kinase) 2 kinase, is activated in the rat carotid artery after balloon angioplasty injury, and may mediate smooth muscle proliferation. To test the hypothesis that inhibition of the expression of this ... Full text Link to item Cite

Angiotensin converting enzyme and genetic hypertension: cloning of rat cDNAs and characterization of the enzyme.

Journal Article Biochem Biophys Res Commun · January 14, 1994 Using genetic mapping approaches, a gene on chromosome 10, Bp1, has been identified in the stroke-prone spontaneously hypertensive rat (SHRSP) in the same region that contains the gene for angiotensin converting enzyme (ACE). Since ACE plays an important r ... Full text Link to item Cite

Foreword

Chapter · January 1, 1994 Cite

Angiotensin as local modulating factor in ventricular dysfunction and failure due to coronary artery disease.

Journal Article Drugs · 1994 Congestive heart failure is the end product of a progressive series of events resulting from acute myocardial damage. Circulatory neurohormonal systems are activated during the acute phase of left ventricular dysfunction resulting from initial myocardial d ... Full text Link to item Cite

Overview

Journal Article Journal of Hypertension · January 1, 1994 Full text Cite

Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.

Journal Article J Clin Invest · January 1994 Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro. Consistent with this, Ang II enhances neointimal proliferation in vivo after vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate this process. Sin ... Full text Link to item Cite

H19, a developmentally regulated gene, is reexpressed in rat vascular smooth muscle cells after injury.

Journal Article J Clin Invest · January 1994 Vascular smooth muscle cell migration, proliferation, and differentiation are central to blood vessel development. Since neointimal formation after vascular injury may require the reexpression of a smooth muscle developmental sequence, we examined the expr ... Full text Link to item Cite

Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor.

Journal Article Biochem Biophys Res Commun · December 15, 1993 A cDNA clone encoding the mouse angiotensin receptor subtype 2 (AT2 receptor) was isolated from a mouse fetal cDNA library. Mouse AT2 receptor full-length cDNA contains a 1089-base-pair open reading frame which encodes a protein of 363 amino acid residues. ... Full text Link to item Cite

Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors.

Journal Article J Biol Chem · November 25, 1993 Angiotensin II acts on at least two distinct receptor subtypes (AT1 and AT2). Most known effects of angiotensin II in adult tissues are attributable to the AT1 receptor. The function of AT2 receptor is undefined, but its abundant expressions in fetal tissu ... Link to item Cite

Structure and function of academic divisions of cardiology. Task Force Reports from the Association of Professors of Cardiology.

Journal Article Arch Intern Med · October 25, 1993 The discipline of cardiovascular medicine has undergone a striking transformation in recent decades. The field has always been of primary importance in medicine, because of the high prevalence of diseases of the cardiovascular system. However, progress in ... Full text Link to item Cite

Distinct nuclear proteins competing for an overlapping sequence of cyclic adenosine monophosphate and negative regulatory elements regulate tissue-specific mouse renin gene expression.

Journal Article J Clin Invest · October 1993 The mouse renin locus (Ren-1d) exhibits specific patterns of tissue expression. It is expressed in kidney but not submandibular gland (SMG). This locus contains a negative regulatory element (NRE) and a cAMP responsive element (CRE) that share an overlappi ... Full text Link to item Cite

Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

Journal Article J Clin Invest · October 1993 Fluid shear stress has been shown to be an important regulator of vascular structure and function through its effect on the endothelial cell. We have explored the effect of shear stress on the expression of the heparin-binding growth factors platelet-deriv ... Full text Link to item Cite

Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia.

Journal Article Proc Natl Acad Sci U S A · September 15, 1993 To develop an effective strategy to prevent neointima formation after angioplasty injury, we have identified cell-cycle regulatory proteins as targets for inhibition by using antisense oligonucleotides (ODNs). We utilized an intraluminal molecular delivery ... Full text Link to item Cite

Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein coupling.

Journal Article Circulation · July 1993 BACKGROUND: The endothelium acts as the sensor of shear stress and as the mediator of flow-induced changes in vessel tone and structure. The purpose of this study was to delineate the signal transduction pathway of flow-induced release of endothelium-deriv ... Full text Link to item Cite

Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells.

Journal Article Hypertension · June 1993 Although many in vitro gene transfer methods already exist, such as calcium phosphate precipitation, electroporation, or cationic liposomes, these methods cause significant cell injury and cell death. The study of the biology of endogenous autocrine-paracr ... Full text Link to item Cite

Novel and effective gene transfer technique for study of vascular renin angiotensin system.

Journal Article J Clin Invest · June 1993 Vascular renin angiotensin system (RAS) has been reported to exist in vascular wall. However, there is no direct evidence whether the vascular RAS per se can modulate growth of vascular smooth muscle cells (VSMC), because there is no suitable method to inv ... Full text Link to item Cite

Gene therapy for cardiovascular disease.

Journal Article Trends Biotechnol · May 1993 Full text Link to item Cite

Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction.

Journal Article J Clin Invest · May 1993 Activation of tissue-specific gene expression of the components of the renin-angiotensin system (RAS) in humans may play an important role in cardiovascular regulation and pathophysiology. Studies of human tissue RAS expression, however, have been limited ... Full text Link to item Cite

Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat.

Journal Article Cardiovasc Res · May 1993 OBJECTIVE: Activation of the intrarenal renin-angiotensin system may contribute to the pathophysiology of heart failure by accelerating the generation of angiotensin II at local sites within the kidneys. Activation of the local intrarenal renin-angiotensin ... Full text Link to item Cite

Local contractile and growth modulators in the myocardium.

Journal Article Clin Cardiol · May 1993 Symptomatic congestive heart failure is the culmination of a process that evolves over many years. The long preclinical, or "incubation," period is the setting for a broad range of so-called local activities, including those involved in myocardial remodeli ... Full text Link to item Cite

Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II.

Journal Article J Clin Invest · May 1993 Angiotensin (Ang) II stimulates hypertrophic growth of vascular smooth muscle cells (VSMC). Accompanying this growth is the induction of the expression of growth-related protooncogenes (c-fos, c-jun, and c-myc), as well as the synthesis of the autocrine gr ... Full text Link to item Cite

Tissue renin-angiotensin system in myocardial hypertrophy and failure.

Journal Article Arch Intern Med · April 26, 1993 The renin-angiotensin system traditionally has been conceived as a neuroendocrine system functioning in the circulation. Recent research has confirmed the existence of autocrine/paracrine tissue renin-angiotensin systems present and functioning at multiple ... Link to item Cite

Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications.

Journal Article J Hypertens Suppl · April 1993 AIM: To examine the nature of multiple putative enzymatic pathways, review the evidence of angiotensin receptor heterogeneity and speculate on the implications for physiology and pharmacology. METHOD: Literature review and discussion of current research. R ... Link to item Cite

Differential effects of antihypertensive agents in experimental and human atherosclerosis.

Journal Article Am J Hypertens · March 1993 The association between hypertension and atherosclerosis is complex, incorporating endothelial dysfunction, abnormalities of insulin and lipid metabolism, altered vascular biology, and impaired arterial compliance. Results of experimental and human studies ... Full text Link to item Cite

Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II.

Journal Article Circ Res · February 1993 Although renin and angiotensinogen are known to be subject to feedback regulation, the effects of angiotensin II (Ang II) on the regulation of angiotensin converting enzyme (ACE) gene expression and enzymatic activity have not yet been studied. Therefore, ... Full text Link to item Cite

Vascular renin-angiotensin system and vascular protection

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1993 Full text Cite

S-nitrosocaptopril: A novel nitrovasodilator resistant to nitrate tolerance

Journal Article Journal of Vascular Medicine and Biology · January 1, 1993 We recently synthesized the molecule, S-nitrosocaptopril, and demonstrated that this molecule combines the properties of a nitrovasodilator and angiotensin-converting enzyme inhibitor. Similarly to other nitrovasodilators, it inhibits platelet aggregation ... Cite

The renin-Angiotensin system and vascular protection: Introduction

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1993 Cite

Vascular remodeling: mechanisms and implications.

Journal Article J Cardiovasc Pharmacol · 1993 It is now recognized that, in addition to being able to change its tone acutely, the blood vessel is capable of altering its structure chronically in response to specific conditions. This is mediated by vascular remodeling, an active process that results i ... Link to item Cite

Vascular renin-angiotensin system and vascular protection.

Journal Article J Cardiovasc Pharmacol · 1993 Vascular angiotensin plays an important role in the long-term regulation of the blood vessel function and structure. Angiotensin stimulates vascular smooth-muscle cell growth via the induction of protooncogene and autocrine growth factor gene expressions. ... Full text Link to item Cite

The role of mechanical and humoral factors in growth regulation of vascular smooth muscle and cardiac myocytes.

Journal Article Curr Opin Nephrol Hypertens · January 1993 Structural changes of the heart and blood vessels participate in the long-term regulation of the cardiovascular system. In hypertension and myocardial dysfunction, the adaptive process of cardiac and vascular remodeling may contribute to the pathophysiolog ... Full text Link to item Cite

Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart.

Journal Article Basic Res Cardiol · 1993 While the circulating renin-angiotensin system (RAS) plays an important role in short-term maintenance of cardiovascular homeostasis, recent studies point to a role in long-term cardiovascular regulation for endogenous RAS in target tissues. This article f ... Full text Link to item Cite

Panel discussion: Question and answer session

Journal Article Clinical Cardiology · January 1, 1993 Full text Cite

Specific blockade of basic fibroblast growth factor gene expression in endothelial cells by antisense oligonucleotide.

Journal Article Biochem Biophys Res Commun · November 16, 1992 The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. To elucidate the role of endogenous basic fibroblast growth factor (bFGF) produced within endothelial cells on cell growth, we introduced the antisense o ... Full text Link to item Cite

Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II.

Journal Article Am J Physiol · November 1992 The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 1 ... Full text Link to item Cite

Differential effects of captopril and enalapril on tissue renin-angiotensin systems in experimental heart failure.

Journal Article Circulation · November 1992 BACKGROUND: Angiotensin converting enzyme (ACE) inhibitor therapy elicits beneficial responses from patients with heart failure. We hypothesized that a major site of action of these drugs is tissue ACE and that ACE inhibitors might differ in their ability ... Full text Link to item Cite

Autocrine and paracrine mechanisms in the pathophysiology of heart failure.

Journal Article Am J Cardiol · October 8, 1992 At the cellular and molecular level the transition to heart failure is a complex process that involves structural adaptation, not only of the heart, but of peripheral vasculature and renal tissues as well. Recent studies have suggested that autocrine, para ... Full text Link to item Cite

The heart in hypertension.

Journal Article N Engl J Med · October 1, 1992 Full text Link to item Cite

Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure.

Journal Article J Clin Invest · October 1992 The intrarenal renin-angiotensin system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, ... Full text Link to item Cite

L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.

Journal Article J Clin Invest · October 1992 Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nit ... Full text Link to item Cite

Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II.

Journal Article J Clin Invest · August 1992 Recent observations in our laboratory suggest that angiotensin II (Ang II) is a bifunctional vascular smooth muscle cell (VSMC) growth modulator capable of inducing hypertrophy or inhibiting mitogen-stimulated DNA synthesis. Because transforming growth fac ... Full text Link to item Cite

Characterization of nuclear angiotensin-II-binding sites in rat liver and comparison with plasma membrane receptors.

Journal Article Endocrinology · July 1992 Although the action of angiotensin-II (Ang-II) is believed to be mediated by a transmembrane signal transduction mechanism, accumulating evidence suggests that Ang-II may also have a direct nuclear action. We have characterized the nuclear Ang-II-binding s ... Full text Link to item Cite

Angiotensin converting enzyme inhibitors and the cardiovascular system.

Journal Article J Hypertens Suppl · June 1992 OBJECTIVE: To show that angiotensin converting enzyme (ACE) inhibitors benefit the cardiovascular system to a greater extent than other antihypertensive agents. DATA EXTRACTION: An extensive literature search has shown that ACE inhibitors can induce regres ... Link to item Cite

Autocrine stimulation of mas oncogene leads to altered growth control.

Journal Article Cell Biol Int Rep · June 1992 Mas oncogene has been shown to have focus-inducing ability in NIH 3T3 cells which are tumorigenic in vivo in nude mice. Its stable expression in a variety of cell lines conferred some angiotensin responsiveness. To understand why mas-transfected cells exhi ... Full text Link to item Cite

Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells.

Journal Article Hypertension · June 1992 The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. We have previously reported that atrial natriuretic polypeptide (ANP) exerts an antigrowth effect on vascular smooth muscle cells via the guanylate cycla ... Full text Link to item Cite

Cloning, characterization, and expression of two angiotensin receptor (AT-1) isoforms from the mouse genome.

Journal Article Biochem Biophys Res Commun · May 29, 1992 We report the existence of two structurally distinct forms of the angiotensin receptor AT-1 in the mouse. A Balb/c mouse genomic library was screened by homology screening with a polymerase chain reaction (PCR) amplified probe. Restriction mapping and sequ ... Full text Link to item Cite

Tissue specificity of renin promoter activity and regulation in mice.

Journal Article Am J Physiol · May 1992 Certain mouse strains (e.g., DBA/2) contain two renin genes (termed Ren-1 and Ren-2) and express higher renin levels in nonkidney tissues than strains with a single renin gene. The 5'-flanking regions of the Ren-1 and Ren-2 genes contain several TATA boxes ... Full text Link to item Cite

Genetic mapping in hypertension.

Journal Article J Vasc Surg · May 1992 Full text Link to item Cite

Characterization of a monoclonal antibody specific for human active renin.

Journal Article Hypertension · March 1992 We have identified and characterized an anti-human renin monoclonal antibody R1-20-5 that is selective for human active renin. R1-20-5 binds active renin with a dissociation constant (Kd) of 2.5 x 10(-7) M/l and inhibits renin enzymatic activity with an in ... Full text Link to item Cite

Identification of a negative regulatory element involved in tissue-specific expression of mouse renin genes.

Journal Article Proc Natl Acad Sci U S A · February 1, 1992 The 5' flanking region of the mouse renin genes (Ren-1d and Ren-2d) contains two motifs that are homologous to known negative regulatory elements (NREs). Ren-2d has a 150-base-pair (bp) insertion 5' to the upstream putative NRE (NRE-1), which is lacking in ... Full text Link to item Cite

Cell-dependent posttranslational processing and secretion of recombinant mouse renin-2.

Journal Article Am J Physiol · February 1992 In the DBA/2 mouse submandibular gland (SMG), renin is predominantly the expression product of the renin gene Ren-2d. Prorenin is synthesized and rapidly converted to a constitutively secreted single-chain intermediate, which is then processed to and store ... Full text Link to item Cite

Effect of isradipine on cardiopulmonary baroreflex function, regional blood flow, and vascular responsiveness in hypertensive patients.

Journal Article J Cardiovasc Pharmacol · February 1992 Calcium channel antagonists, when used to treat hypertension, may modulate baroreflex function and vascular responsiveness to endogenous vasoconstrictors. We studied regional blood flow, cardiopulmonary baroreflex function, and pressor responses in nine hy ... Full text Link to item Cite

Working group on noncoronary cardiovascular disease and exercise in women

Journal Article Medicine and Science in Sports and Exercise · 1992 Cite

Effect of captopril on the release of the components of the renin-angiotensin system into plasma and lymph.

Journal Article J Am Soc Nephrol · January 1992 UNLABELLED: The effects of captopril on the intrarenal renin-angiotensin system were assessed from measurements in arterial plasma, renal venous plasma, and renal lymph from salt-depleted dogs. In the basal state, immunoreactive angiotensin II (Ang II) in ... Full text Link to item Cite

The guide to cardiology: Evaluation and management of hypertension

Journal Article Cardiovascular Reviews and Reports · January 1, 1992 Data from the National Health and Nutrition Examination Survey indicate that approximately 58 million Americans are at increased risk for morbidity and premature death from high blood pressure. Effective treatment for hypertension requires measurement of t ... Cite

Mas oncogene receptor coupling and peptide specificity in Balb 3T3 and vascular smooth muscle cells.

Journal Article Am J Med Sci · December 1991 The mas oncogene receptor has been reported to confer angiotensin (Ang) responsiveness in NG115-401L neuronal cell line. To test if mas oncogene encodes an Ang receptor in peripheral tissue, Balb 3T3 and rat aortic vascular smooth muscle cells (VSMC) were ... Full text Link to item Cite

Introduction: Atherosclerosis beyond cholesterol

Journal Article Journal of Vascular Medicine and Biology · December 1, 1991 Cite

Differential effects of antihypertensive agents in experimental and human atherosclerosis

Journal Article Journal of Vascular Medicine and Biology · December 1, 1991 The association between hypertension and atherosclerosis is complex, incorporating endothelial dysfunction, abnormalities of insulin and lipid metabolism, altered vascular biology, and impaired arterial compliance. Results of experimental and human studies ... Cite

Endothelium and growth factors in vascular remodeling of hypertension.

Journal Article Hypertension · November 1991 The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothe ... Full text Link to item Cite

Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator.

Journal Article J Clin Invest · November 1991 Flow-mediated vasodilation is endothelium dependent. We hypothesized that flow activates a potassium channel on the endothelium, and that activation of this channel leads to the release of the endogenous nitrovasodilator, nitric oxide. To test this hypothe ... Full text Link to item Cite

Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat.

Journal Article Cell · October 4, 1991 The stroke-prone spontaneously hypertensive rat (SHRSP) is a well-characterized model for primary hypertension in humans. High blood pressure in SHRSP shows polygenic inheritance, but none of the loci responsible have previously been identified. To locate ... Full text Link to item Cite

Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia.

Journal Article Hypertension · October 1991 Angiotensin II has been shown by many investigators to be a potent growth factor for vascular smooth cells in culture as well as in vivo. Depending on the conditions, the response of these cells is either hypertrophy or hyperplasia. These observations have ... Full text Link to item Cite

Molecular biology of hypertension.

Journal Article Hypertension · September 1991 Hypertension results from abnormalities of the control systems that normally regulate blood pressure. These control systems include vascular, cardiogenic, renal, neurogenic, and endocrine mechanisms that interact in a complex but integrated manner to achie ... Full text Link to item Cite

Molecular mechanism of tissue-specific regulation of mouse renin gene expression by cAMP. Identification of an inhibitory protein that binds nuclear transcriptional factor.

Journal Article J Biol Chem · August 25, 1991 Renin gene expression in the mouse kidney and submandibular gland (SMG) are differentially regulated by cAMP. In this study, we examined the potential molecular mechanism responsible for this tissue-specific regulation. 32P end-labeled synthetic oligonucle ... Link to item Cite

Molecular biology of renal injury: emphasis on the role of the renin-angiotensin system.

Journal Article J Am Soc Nephrol · August 1991 The developments in molecular biology of the past decade have created a powerful technology with important, if not revolutionary, clinical applications. This review discusses the molecular biology of renal injury focusing on the renin-angiotensin system as ... Full text Link to item Cite

Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure.

Journal Article Circ Res · August 1991 In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-ang ... Full text Link to item Cite

Renin promoter SV40 T-antigen transgenic mouse. A model of primary renal vascular hyperplasia.

Journal Article Hypertension · June 1991 Transgenic mice containing a ren-2 promoter T-antigen fusion construct (TAG+) develop renal vascular hypertrophy and hyperplasia associated with markedly suppressed renal renin mRNA, renal renin content, and plasma renin concentration. These animals are no ... Full text Link to item Cite

Sodium depresses arterial baroreceptor reflex function in normotensive humans.

Journal Article Hypertension · June 1991 Sodium may contribute to the pathogenesis of hypertension by impairing arterial baroreceptor reflex function. The objectives of this study were to 1) determine whether a high sodium diet depresses arterial baroreceptor reflex function in normotensive human ... Full text Link to item Cite

Characterization of prorenin activation using a synthetic peptide substrate.

Journal Article J Hypertens · June 1991 Human renin is synthesized as an inactive zymogen (prorenin) which is processed to the active form. We synthesized an 11-amino acid peptide which spans the human prorenin processing site in order to develop a simple assay to study human prorenin activation ... Full text Link to item Cite

Interaction of atrial natriuretic polypeptide and angiotensin II on protooncogene expression and vascular cell growth.

Journal Article Biochem Biophys Res Commun · May 15, 1991 Recent evidence suggests that vasoconstrictive substances, including angiotensin II (Ang II), may function as a vascular smooth muscle growth promoting substance and may contribute to vascular hypertrophy in hypertension. Atrial natriuretic polypeptide (AN ... Full text Link to item Cite

Renin and myocardial infarction in hypertension.

Journal Article N Engl J Med · April 18, 1991 Full text Link to item Cite

Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement.

Journal Article Am Heart J · April 1991 Advances in cardiovascular research during the past two decades have resulted in an improved understanding of the chain of events that lead to end-stage coronary artery disease. These developments have been paralleled by therapeutic advances that now make ... Full text Link to item Cite

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Journal Article J Clin Invest · April 1991 Recent data demonstrate the existence of a vascular renin angiotensin system. In this study we examine the localization of angiotensinogen mRNA in the blood vessel wall of two rat strains, the Wistar and Wistar Kyoto (WKY), as well as the regulation of vas ... Full text Link to item Cite

Workshop IX--Lipids, insulin, diabetes.

Journal Article Am J Med · February 21, 1991 Full text Link to item Cite

Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice.

Journal Article Am J Physiol · February 1991 The pathophysiological consequence of targeted production of SV-40 T-antigen to renin-expressing cells in the kidney of transgenic mice is reported. A histopathologic analysis of the kidney from adult transgenic mice (12-16 wk old) revealed the presence of ... Full text Link to item Cite

Molecular biology of hypertension

Journal Article Hypertension · January 1, 1991 Hypertension results from abnormalities of the control systems that normally regulate blood pressure. These control systems include vascular, cardiogenic, renal, neurogenic, and endocrine mechanisms that interact in a complex but integrated manner to achie ... Cite

Endothelial dysfunction in hypercholesterolemia is corrected by L-arginine.

Journal Article Basic Res Cardiol · 1991 Hypercholesterolemia attenuates endothelium-dependent vasorelaxation and augments the responses to vasoconstrictor agents. Both effects are largely due to a reduction in the release of endothelium-derived relaxing factor. Since endothelium-derived relaxing ... Full text Link to item Cite

Recent advances in the control of heart failure: Introduction

Journal Article American Heart Journal · January 1, 1991 Full text Cite

Evolving concepts of the intrarenal renin-angiotensin system in health and disease: contributions of molecular biology.

Journal Article Ren Physiol Biochem · 1991 Previous physiological and biochemical studies suggest the existence of an endogenous renin-angiotensin system (RAS) in the kidney. However, these data cannot exclude the contribution of the circulating RAS. Proof of the local synthesis of RAS components i ... Full text Link to item Cite

Endothelium and growth factors in vascular remodeling of hypertension

Journal Article Hypertension · 1991 The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothe ... Cite

The guide to cardiology: Heart failure

Journal Article Cardiovascular Reviews and Reports · January 1, 1991 Cite

Role of angiotensin in the control of vascular smooth muscle growth

Journal Article Journal of Vascular Medicine and Biology · January 1, 1991 Cite

Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.

Journal Article J Clin Invest · December 1990 We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response t ... Full text Link to item Cite

L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits.

Journal Article Circ Res · December 1990 Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo i ... Full text Link to item Cite

Angiotensin II can regulate gene expression by the AP-1 binding sequence via a protein kinase C-dependent pathway.

Journal Article Biochem Biophys Res Commun · November 15, 1990 An expression vector containing three copies of the AP-1 binding element (TRE) upstream of a thymidine kinase promotor which controlled the expression of the chloramphenicol acetyl transferase (CAT) gene was transiently transfected into vascular smooth mus ... Full text Link to item Cite

Isolation and characterization of renin-expressing cell lines from transgenic mice containing a renin-promoter viral oncogene fusion construct.

Journal Article J Biol Chem · November 15, 1990 We constructed transgenic mice containing a renin-promoter SV40 T antigen fusion transgene with the intention of inducing neoplasia in renin-expressing cells and isolating renin-expressing cell lines in vitro. We examined six kidney tumors from mice repres ... Link to item Cite

Atrial natriuretic polypeptide inhibits hypertrophy of vascular smooth muscle cells.

Journal Article J Clin Invest · November 1990 Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. Recent evidence suggests that vasoconstrictive substances, such as angiotensin II (AII), may function as a vascular smooth muscle growth promoting substance. To expl ... Full text Link to item Cite

Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure.

Journal Article Am J Cardiol · October 2, 1990 The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This art ... Full text Link to item Cite

Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.

Journal Article J Clin Invest · July 1990 The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholestero ... Full text Link to item Cite

Intrarenal angiotensinogen: localization and regulation.

Journal Article Pediatr Nephrol · July 1990 Multiple lines of evidence (physiologic, immunohistochemical, and molecular biologic) support the presence of a complete intrarenal renin-angiotensin system (RAS). Localization of angiotensinogen messenger ribonucleic acid (mRNA) within the proximal tubule ... Full text Link to item Cite

Baroreflex regulation of regional blood flow in congestive heart failure.

Journal Article Am J Physiol · May 1990 In patients with congestive heart failure (CHF), the distribution of the cardiac output is altered. Cardiopulmonary and arterial baroreceptors normally can regulate regional blood flow, but their contribution in heart failure is not known. To examine the r ... Full text Link to item Cite

Angiotensin converting enzyme inhibition and vascular hypertrophy in hypertension.

Journal Article Cardiovasc Drugs Ther · February 1990 The pathogenesis of hypertension is associated with a remodeling of vascular structure. Follow has postulated that the decreased luminal area and thickened medial layer in hypertensive vessels enhances the vasoconstrictive response to vasoactive agents. It ... Full text Link to item Cite

In situ hybridization evidence for angiotensinogen messenger RNA in the rat proximal tubule. An hypothesis for the intrarenal renin angiotensin system.

Journal Article J Clin Invest · February 1990 We examined angiotensinogen gene expression in rat kidney by in situ hybridization histochemistry. Using a rat cRNA probe to angiotensinogen, we demonstrated angiotensinogen mRNA to be localized predominantly in the proximal renal tubule, with considerably ... Full text Link to item Cite

The time has come for vascular medicine.

Journal Article Ann Intern Med · January 15, 1990 Advances in the diagnosis and treatment of patients with vascular disorders have led to the emergence of a new kind of internist with special skills in vascular medicine. The growth of this field will accelerate as recent major advances in vascular biology ... Full text Link to item Cite

Introduction

Chapter · January 1, 1990 Full text Cite

Summary

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1990 Full text Cite

Mechanism of action of angiotensin-converting enzyme (ACE) inhibitors in hypertension and heart failure. Role of plasma versus tissue ACE.

Journal Article Drugs · 1990 The contribution of plasma versus tissue angiotensin-converting enzyme (ACE) to pathophysiology and drug effect is reviewed. The data suggest that tissue ACE is important in influencing local angiotensin levels and that the long term response to an ACE inh ... Full text Link to item Cite

Atherosclerosis and hypertension: mechanisms and interrelationships.

Journal Article J Cardiovasc Pharmacol · 1990 Hypertension, dyslipidemia, and glucose intolerance cocluster in the population and act synergistically in increasing coronary artery disease risk. The mechanisms by which these risk factors interact in atherosclerosis are complex. First, hypertension, dys ... Link to item Cite

Worldwide clinical experience with ACE inhibitors. The role of quinapril: introduction

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1990 Cite

World wide clinical experience with ACE inhibitors. The role of quinapril: summary

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1990 Cite

Paracrine renin angiotensin system in the kidney: Molecular evidence and functional significance

Journal Article Frontiers of Nephrology Proceedings of the International Forum the Frontiers of Nephrology Honoring Fuminori Sakai Ics877 · January 1, 1990 The recent demonstrations of renin, angiotensinogen and angiotensin converting enzyme mRNAs in the kidney provide strong evidence for the presence of an independent intrarenal RAS. Using in situ hybridization, we have localized the intrarenal sites of gene ... Cite

Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion.

Journal Article Circ Res · January 1990 Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-p ... Full text Link to item Cite

Multiple pathways of angiotensin production in the blood vessel wall: evidence, possibilities and hypotheses.

Journal Article J Hypertens · December 1989 In summary, multiple pathways of angiotensin production may exist in the blood vessel wall (Fig. 1), in addition to the well described renin--ACE enzymatic axis. It is not known whether these enzymatic pathways represent in vitro phenomena, or authentic in ... Full text Link to item Cite

A lack of genetic linkage of renin gene restriction fragment length polymorphisms with human hypertension.

Journal Article Hypertension · December 1989 Because renin is an important enzyme in blood pressure regulation, we studied the possibility that an alteration in the structure of the human renin gene is genetically linked to human essential hypertension or associated with levels of plasma renin activi ... Full text Link to item Cite

Atrial natriuretic factor-specific antibody as a tool for physiological studies. Evidence for role of atrial natriuretic factor in aldosterone and renal electrolyte regulation.

Journal Article Circ Res · November 1989 Numerous studies have shown that administration of atrial natriuretic factor (ANF) increases urinary sodium excretion and urine flow, decreases blood pressure, and inhibits renin and aldosterone release. However, the role of endogenous ANF in the regulatio ... Full text Link to item Cite

Molecular biology and pathophysiology of the intrarenal renin-angiotensin system.

Journal Article J Hypertens Suppl · September 1989 There has been considerable interest in the existence of an intrarenal renin-angiotensin system and its physiological implications. Recent demonstrations of renin, angiotensinogen and angiotensin converting enzyme messenger (m)RNAs in the kidney have provi ... Full text Link to item Cite

Vasopressin-mediated forearm vasodilation in normal humans. Evidence for a vascular vasopressin V2 receptor.

Journal Article J Clin Invest · August 1989 Arginine vasopressin (AVP) is a potent vasopressor and antidiuretic neurohormone. However, when administered intravenously to humans, AVP causes forearm vasodilation. This effect has been attributed to sympathetic withdrawal, secondary to AVP-induced sensi ... Full text Link to item Cite

Regional vascular responses to prolonged lower body negative pressure in normal subjects.

Journal Article Am J Physiol · July 1989 The purpose of this study was to determine the effects of sustained unloading of baroreceptors in humans. The regional hemodynamic responses to lower body negative pressure (LBNP) were determined in 20 normal subjects. LBNP at -10 mmHg for 1 h decreased ce ... Full text Link to item Cite

Angiotensin II induces c-fos expression in smooth muscle via transcriptional control.

Journal Article Hypertension · June 1989 Angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle cells. This observation along with the recent demonstration of angiotensinogen messenger RNA (mRNA) in the vessel wall has led us to postulate a role ... Full text Link to item Cite

Role of molecular biology in hypertension research. State of the Art lecture.

Journal Article Hypertension · June 1989 In this article we will examine the potential impact of molecular biology on hypertension research. We will review the available molecular techniques, which include gene cloning, transient and stable expressions, as well as the use of transgenic animals. T ... Full text Link to item Cite

Androgen regulation of rat renal angiotensinogen messenger RNA expression.

Journal Article J Clin Invest · June 1989 Renal angiotensinogen (ang-n) mRNA concentration in the male WKY rat increases significantly during puberty. Furthermore, renal angiotensinogen mRNA level in the adult female WKY rat is considerably lower than in the male. The present study investigates th ... Full text Link to item Cite

Identification of negative and positive regulatory elements in the human renin gene.

Journal Article J Biol Chem · May 5, 1989 Renin gene expression is tissue-specific and under complex hormonal control. To investigate which DNA elements are involved in the control of human renin gene expression, we performed transient DNA transfer experiments with renin-chloramphenicol acetyltran ... Link to item Cite

Synthetic peptide inhibitors of prorenin activation.

Journal Article J Hypertens Suppl · April 1989 In studying potential inhibitors of prorenin activation, we synthesized stereoisomers of a nonapeptide which spans the putative prorenin cleavage site. Peptide 67 has a D-Leu substitution on the amino side of the sessile bond and peptide 68 has a D-Arg sub ... Full text Link to item Cite

Processing of one-chain to two-chain renin in the mouse submandibular gland is influenced by androgen.

Journal Article Pediatr Res · April 1989 In the male CD-1 mouse submandibular gland (SMG) renin activity increases markedly with puberty. We have reported that this is, in part, due to an androgen-mediated increase in renin gene transcription. In this study, we examined whether posttranslational ... Full text Link to item Cite

Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells.

Journal Article J Clin Invest · April 1989 Recently, angiotensin II (Ang II) has been shown to cause hypertrophy of cultured quiescent rat aortic smooth muscle (RASM) cells. This observation along with the demonstration of angiotensinogen mRNA in the vessel wall has led us to postulate a role for v ... Full text Link to item Cite

Altered sodium regulation of renal angiotensinogen mRNA in the spontaneously hypertensive rat.

Journal Article Am J Physiol · March 1989 The expression of the intrarenal renin angiotensin mRNAs in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were investigated in rats fed a low (0.02%)- or normal (1.6%)-sodium diet for 5 days. Total RNA was isolated from the kidneys and ... Full text Link to item Cite

Progress in angiotensin-converting enzyme inhibition in heart failure: rationale, mechanisms, and clinical responses.

Journal Article Cardiol Clin · February 1989 The pharmacology and mechanisms of action of angiotensin-converting enzyme (ACE) inhibitors are reviewed in this article together with discussions on their acute and hemodynamic effects; influence on regional blood flow and renal responses; clinical effica ... Link to item Cite

Effects of alpha- and beta-adrenergic antagonists on plasma apolipoproteins and forearm blood flow in patients with mild hypertension.

Journal Article Am J Med · January 23, 1989 To study the mechanisms by which adrenergic antagonists affect blood pressure and plasma lipid levels, the effects of alpha-blockade with prazosin were compared with those of beta-blockade with propranolol in 23 normolipidemic, mildly hypertensive patients ... Full text Link to item Cite

Relation of atrial natriuretic factor to vasoconstrictor hormones and regional blood flow in congestive heart failure.

Journal Article Am J Cardiol · January 15, 1989 Plasma levels of both atrial natriuretic factor (ANF) and vasoconstrictor neurohormones are often increased in patients with congestive heart failure (CHF). It has been speculated that ANF is a counterregulatory hormone that influences regional blood flow ... Full text Link to item Cite

Introduction

Chapter · January 1, 1989 Full text Cite

Short- and long-term determinants of cardiovascular function and therapy: contributions of circulating and tissue renin-angiotensin systems.

Journal Article J Cardiovasc Pharmacol · 1989 Cardiovascular function is regulated by short-term and long-term neurohormonal and autocrine-paracrine mechanisms that act synergistically or sequentially. Structural adaptive changes that occur progressively over time also contribute to the long-term outc ... Link to item Cite

Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes.

Journal Article Proc Natl Acad Sci U S A · January 1989 The 5' flanking regions of the mouse renin genes (Ren1d and Ren2d) contain putative negative control and cAMP responsive elements. Sequence analysis shows additionally that these putative control elements in the Ren2d gene are interrupted by a 160-base-pai ... Full text Link to item Cite

Cardiovascular hemostasis. Effects of circulating and local renin-angiotensin-system

Journal Article Munchener Medizinische Wochenschrift · January 1, 1989 Cite

Clinical implications for therapy: possible cardioprotective effects of ACE inhibition.

Journal Article Br J Clin Pharmacol · 1989 1. The circulating and tissue renin-angiotensin systems (RAS) contribute importantly to cardiovascular homeostasis. Systemic and/or local activation of the RAS is seen in many pathological conditions of the cardiovascular system (e.g. hypertension and cong ... Full text Link to item Cite

ACE inhibitors in hypertension: a US perspective.

Journal Article Cardiology · 1989 The failure of recent antihypertensive trials to document clearly a reduction in the risk of coronary heart disease (nonfatal or fatal myocardial infarction and sudden death) has important clinical implications. Although the causes of this phenomenon are u ... Full text Link to item Cite

Glycosylation influences intracellular transit time and secretion rate of human prorenin in transfected cells.

Journal Article J Hypertens Suppl · December 1988 The mouse pituitary tumour (AtT-20) cell transfected with the human renin gene has been shown to be a useful model system to study human renin biosynthesis. To investigate the influence of glycosylation on secretion of human renin from these cells, we perf ... Full text Link to item Cite

Functional human renin promoter in transfected cells: evidence for cell-specific expression.

Journal Article J Hypertens Suppl · December 1988 Expression of the human renin gene is regulated in a tissue-specific manner, but study of this regulation has been limited by a lack of suitable cell lines that simulate endogenous control. In order to characterize the regulation of renin gene expression, ... Full text Link to item Cite

The international standard for atrial natriuretic factor. Calibration by an international collaborative study.

Journal Article Hypertension · December 1988 An ampouled preparation of human atrial natriuretic factor, ANF-(99-126), was evaluated by 23 laboratories in 10 countries for its suitability to serve as the international standard for ANF. The preparation was calibrated by radioimmunoassay, radioreceptor ... Full text Link to item Cite

Molecular and physiological aspects of tissue renin-angiotensin system: emphasis on cardiovascular control.

Journal Article J Hypertens Suppl · December 1988 Angiotensin II (Ang II), an important peptide in cardiovascular physiology, is the product of enzymatic processing of angiotensinogen which involves two proteolytic steps carried out by renin and angiotensin converting enzyme (ACE) sequentially. This syste ... Link to item Cite

Mechanism of the interaction of hypertension and hypercholesterolemia in atherogenesis: the effects of antihypertensive agents.

Journal Article Am Heart J · December 1988 Any alteration in the balance between serum lipids, platelets, hemodynamic factors, and the blood vessel wall may lead to the development of atherosclerosis. Hypertension and hypercholesterolemia are two major risk factors that accelerate the development o ... Full text Link to item Cite

Cell biology of vascular hypertrophy in systemic hypertension.

Journal Article Am J Cardiol · October 5, 1988 Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function (i.e., structur ... Full text Link to item Cite

Molecular biology of the renin-angiotensin system.

Journal Article Am J Physiol · October 1988 This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the com ... Full text Link to item Cite

Evidence for two cellular pathways of renin secretion by the mouse submandibular gland.

Journal Article Endocrinology · October 1988 The pathway of renin secretion has been defined in the mouse submandibular gland (SMG). Renin is first synthesized as a prorenin, rapidly cleaved to a one-chain renin, and then very slowly processed to a two-chain form which is stored in mature granules. I ... Full text Link to item Cite

Evolving concepts of the renin-angiotensin system. Focus on renal and vascular mechanisms.

Journal Article Am J Hypertens · October 1988 The traditional concept of the renin-angiotensin system (RAS) is a circulation-borne endocrine system, the components of which are secreted by various organs. The product of this biochemical cascade, angiotensin II, acts on specific receptors on multiple t ... Full text Link to item Cite

Contributions of neuroendocrine and local autocrine-paracrine mechanisms to the pathophysiology and pharmacology of congestive heart failure.

Journal Article Am J Cardiol · September 9, 1988 The degree of activation of neurohormonal mechanisms appears to depend on the severity and acuteness of cardiac impairment as well as the status of the extracellular fluid volume. Vasoconstrictive antinatriuretic mechanisms are markedly activated in severe ... Full text Link to item Cite

Circulating versus local renin-angiotensin system in cardiovascular homeostasis.

Journal Article Circulation · June 1988 The renin-angiotensin system has traditionally been viewed as an endocrine system. Recent data demonstrate that renin and angiotensinogen genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesize angiot ... Link to item Cite

Responsiveness of atrial natriuretic factor to reduction in right atrial pressure in patients with chronic congestive heart failure.

Journal Article J Am Coll Cardiol · June 1988 In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vas ... Full text Link to item Cite

Vascular and renal prostaglandins as counter-regulatory systems in heart failure.

Journal Article Eur Heart J · June 1988 Vasoconstrictors and vasodilators are both activated in patients with severe heart failure. Vasodilatory prostaglandins are increased in parallel with the degree of activation of neurohumoral vasoconstrictor systems, and may serve to offset the circulatory ... Full text Link to item Cite

Vascular renin-angiotensin system in hypertension. New insights into the mechanism of action of angiotensin converting enzyme inhibitors.

Journal Article Am J Med · April 15, 1988 Evidence is accumulating that demonstrates the presence of local renin-angiotensin systems, in addition to the established circulating renin-angiotensin system. Renin-like substances, immunoreactive angiotensins, and angiotensin II receptors have been iden ... Full text Link to item Cite

Cardiac renin-angiotensin system. Molecular and functional aspects.

Journal Article Am J Med · March 11, 1988 Current data support the existence of an endogenous renin-angiotensin system in the heart. Vascular angiotensin may contribute to the regulation of coronary vascular tone. Enhanced local angiotensin production in areas of vascular injury or inflammation ma ... Full text Link to item Cite

Different secretory pathways of renin from mouse cells transfected with the human renin gene.

Journal Article J Biol Chem · March 5, 1988 Mammalian cells in culture, transfected with human renin gene, can provide a useful tool for studying renin biosynthesis and secretion. We transfected fibroblast cells (mouse L929 and Chinese hamster ovary cells) and pituitary tumor cells (mouse AtT-20) wi ... Link to item Cite

Regulation of extra-renal renin during ontogeny.

Journal Article Endocrinology · March 1988 Previous studies demonstrated that the level of renin in the male submandibular gland (SMG) of mouse strains that contain renin genes [e.g. Cr1:CD-1(1CR)BR] increased dramatically at puberty, but a less pronounced response was seen in the C57BL/10J (a stra ... Full text Link to item Cite

Plasma atrial natriuretic factor during chronic thoracic inferior vena caval constriction.

Journal Article Circ Res · February 1988 The effects of chronic constriction of the thoracic inferior vena cava (TIVCC) on plasma atrial natriuretic factor (pANF) were studied in conscious dogs (n = 5). TIVCC decreased left and right atrial pressure and led to a decrease in pANF concentration fro ... Full text Link to item Cite

Roundtable discussion one

Journal Article American Journal of Hypertension · January 1, 1988 Full text Cite

Partial purification of a prorenin activating enzyme in the aortic wall.

Journal Article Clin Exp Hypertens A · 1988 The presence of a prorenin activating enzyme in the blood vessel wall may have important physiological implications. The putative enzyme may be involved with the endogenous production of active renin (a key enzyme in the vascular renin angiotensin system) ... Full text Link to item Cite

Mapping of the human renin transcription start site: evidence for a single functional promoter.

Journal Article Clin Exp Hypertens A · 1988 The 5' flanking region of the human renin gene contains two putative promoter sequences (TATA boxes), named P1 and P2. These are located in positions -77 to -71 and -29 to -23 respectively, each followed by a possible translational start site (AUG). In ord ... Full text Link to item Cite

Interactions of neurogenic, circulating and local humoral mechanisms in heart failure

Journal Article TGO Tijdschrift Voor Therapie Geneesmiddel En Onderzoek · January 1, 1988 Cite

Renin gene expression, biosynthesis, and cellular pathways of secretion.

Journal Article Clin Physiol Biochem · 1988 The molecular biology of the human renin gene is reviewed. This 12.5 kb gene contains 10 exons and 9 introns. In its 5' flanking region, major control elements are present. These include promoters and enhancers as well as regulatory elements. The combined ... Link to item Cite

Autocrine-paracrine mechanisms of vascular myocytes in systemic hypertension.

Journal Article Am J Cardiol · December 14, 1987 Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function. The endotheliu ... Full text Link to item Cite

The responses of atrial natriuretic factor concentrations to acute volume changes in conscious rats.

Journal Article Life Sci · November 23, 1987 A rapid and sensitive radioimmunoassay has been developed for measurements of atrial natriuretic factor (ANF) in rat plasma. The antiserum, raised to rat ANF (99-126), cross-reacts with rat ANF (103-123), ANF (103-125), ANF (103-126) but not with smaller f ... Full text Link to item Cite

Dissociation of the prostaglandin and renin angiotensin systems during captopril therapy for chronic congestive heart failure secondary to coronary artery disease.

Journal Article Am J Cardiol · November 1, 1987 Neurohumoral systems are activated as compensatory mechanisms in congestive heart failure (CHF). A close correlation has been reported between the renin angiotensin and prostaglandin systems in CHF. Furthermore, serum sodium concentration provided an excel ... Full text Link to item Cite

Stimulus-response curve of the renal baroreceptor: effect of converting enzyme inhibition and changes in salt intake.

Journal Article Circ Res · November 1987 We investigated the effect of converting enzyme inhibition (CEI) on the relationship between renal perfusion pressure (RPP) and steady-state plasma renin activity (PRA) in uninephrectomized conscious dogs on normal-salt (80 meq Na+/day) and low-salt (10 me ... Full text Link to item Cite

Human renin biosynthesis and secretion in normal and ischemic kidneys.

Journal Article Proc Natl Acad Sci U S A · November 1987 The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradioseque ... Full text Link to item Cite

Relationship of cardiac chamber volume to baroreflex activity in normal humans.

Journal Article J Clin Endocrinol Metab · September 1987 The objectives of this study were to examine the effect of incremental lower body negative pressure (LBNP) on cardiac chamber volume and assess the relationship between cardiac chamber volume and baroreflex activation of the neurohormonal axis. Accordingly ... Full text Link to item Cite

Vascular renin--a consensus view.

Journal Article J Hypertens Suppl · July 1987 Full text Link to item Cite

Inhibition of renin-like activity in marmoset tissues by the renin inhibitor CGP 29 287.

Journal Article J Hypertens Suppl · July 1987 This study investigated the contribution of tissue renin-like activity to the acute hypotensive response induced by the potent and specific inhibitor of primate renin, CGP 29 287. Furosemide-pretreated marmosets (5mg/kg, i.m.) were killed 30 min after bolu ... Full text Link to item Cite

Renal effects of angiotensin-converting enzyme inhibition in cardiac failure.

Journal Article Am J Kidney Dis · July 1987 Compensatory mechanisms such as systemic vasoconstriction and sodium retention are activated to various degrees in patients with congestive heart failure (CHF). The renin-angiotensin system (RAS) mediates many of these compensatory responses. Increased ang ... Link to item Cite

Possible prorenin activating mechanisms in the blood vessel wall.

Journal Article J Hypertens Suppl · July 1987 The blood-vessel wall has the potential for activating circulating prorenin by several mechanisms. Prorenin may be taken up by the blood vessel and activated by enzyme(s) localized on the vascular cells. We do not know whether this mechanism is usually ope ... Full text Link to item Cite

A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues.

Journal Article Endocrinology · June 1987 Previous studies have reported the presence of renin mRNAs in several mouse tissues and angiotensinogen mRNAs in various rat tissues. Clarification as to whether renin and angiotensinogen mRNAs are coexpressed in the same tissues of the same animal species ... Full text Link to item Cite

Tissue-specific regulation of renin expression in the mouse.

Journal Article Hypertension · June 1987 Increasing biochemical evidence suggests that the renin-angiotensin system may be present in may extrarenal tissues. We have employed the mouse submandibular gland renin complementary DNA (pDD-1D2) and the rat liver angiotensinogen complementary DNA (pRang ... Full text Link to item Cite

Nomenclature for atrial peptides.

Journal Article N Engl J Med · May 14, 1987 Full text Link to item Cite

Baroreceptor function in congestive heart failure: effect on neurohumoral activation and regional vascular resistance.

Journal Article Circulation · May 1987 A series of neurohumoral systems are activated in congestive heart failure that contribute to the increased vascular resistance and sodium retention that characterize this disorder. Abnormalities in baroreceptor function are intrinsic to the pathophysiolog ... Link to item Cite

Human neutrophils release serine proteases capable of activating prorenin.

Journal Article Circ Res · April 1987 Proteases from human neutrophils can generate angiotensin II directly from angiotensin I or angiotensinogen. We examined whether neutrophil protease also influences angiotensin formation by activating human prorenin (also called inactive renin). When incub ... Full text Link to item Cite

Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensins.

Journal Article Circ Res · March 1987 Cultured bovine aortic endothelial cells (BAEC) contain renin and angiotensinogen. To examine whether angiotensins are synthesized intracellularly and secreted by these cells, we assayed cell extracts as well as serum-free media of intact confluent BAEC. A ... Full text Link to item Cite

Implications of local angiotensin production in cardiovascular physiology and pharmacology.

Journal Article Am J Cardiol · January 23, 1987 The traditional concept of the renin-angiotensin system is a circulation-borne endocrine system whose components are secreted by different organs, i.e., renin from the kidney, angiotensinogen from the liver and angiotensin-converting enzyme from the lung. ... Full text Link to item Cite

Evolution of the clinical management of hypertension. Emerging role of "specific" vasodilators as initial therapy.

Journal Article Am J Med · January 5, 1987 The primary hemodynamic hallmark of essential hypertension is elevated systemic vascular resistance that may be affected by increased sympathetic tone, activation of the renin-angiotensin system, or structural and cellular abnormalities (e.g., those involv ... Full text Link to item Cite

Evidence for the existence of renin in the heart.

Journal Article Circulation · January 1987 Renin and other components of the renin-angiotensin system have been reported to be present in many extrarenal tissues. We have detected reninlike activities in mouse and rat hearts. Cardiac renin has a pH optimum similar to that of renal renin and its act ... Link to item Cite

Regulation of lipoprotein metabolism by adrenergic mechanisms.

Journal Article J Cardiovasc Pharmacol · 1987 The available data on the adrenergic influences on lipoprotein metabolism are reviewed. It is clear that the influences are complex. It appears that adrenergic stimuli act at multiple sites in the lipoprotein metabolic pathways. This explains in part, the ... Link to item Cite

Vascular angiotensin pathways: a new therapeutic target.

Journal Article J Cardiovasc Pharmacol · 1987 The renin-angiotensin system affects blood pressure and regional blood flow through endocrine, paracrine, and autocrine influences. The circulating endocrine renin-angiotensin system (RAS) is activated for acute cardiovascular homeostasis. The recent demon ... Link to item Cite

Clinical response to angiotensin-converting enzyme inhibition in cardiac failure.

Journal Article Clin Exp Hypertens A · 1987 The renin-angiotensin system plays a pivotal role in the pathophysiology of heart failure. ACE inhibitors block the production of angiotensin II and are efficacious in the therapy of patients with heart failure, ACE inhibitors have combined preload and aft ... Full text Link to item Cite

Characterization of purified rabbit uterine renin: influence of pregnancy on uterine inactive renin.

Journal Article Endocrinology · January 1987 Using specific antibody raised against renal renin, we have documented that the majority of the uterine renin-like activity in gravid and nongravid uteri is immunoreactive renin. To characterize its physiochemical properties, we obtained highly purified ut ... Full text Link to item Cite

Molecular studies of human renin structure and synthesis using monoclonal antibodies.

Journal Article Clin Exp Hypertens A · 1987 Monoclonal antibodies are employed as molecular probes to study human renin structure and synthesis. In this study, we observed that the active site peptide directed antibody did not bind native renin consistent with the hypothesis that the active site is ... Full text Link to item Cite

Sodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla.

Journal Article J Clin Invest · November 1986 Rat liver angiotensinogen cDNA (pRang 3) and mouse renin cDNA (pDD-1D2) were used to identify angiotensinogen and renin mRNA sequences in rat kidney cortex and medulla in rats on high and low salt diet. Angiotensinogen mRNA sequences were present in renal ... Full text Link to item Cite

Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane.

Journal Article Proc Natl Acad Sci U S A · October 1986 Various Ca-channel blockers differ in cardiovascular action despite common effects at the Ca channel. Many investigators have reported only a single high-affinity receptor for binding of [3H]nitrendipine, a dihydropyridine Ca-channel blocker. Its equilibri ... Full text Link to item Cite

Preliminary observations on abnormalities of membrane structure and function in essential hypertension.

Journal Article Hypertension · June 1986 To test the hypothesis that structural abnormalities exist in the cell membrane in persons with essential hypertension and that these abnormalities affect membrane-related cellular functions, we examined several membrane-dependent phenomena and membrane li ... Full text Link to item Cite

Identification of renin and angiotensinogen messenger RNA sequences in mouse and rat brains.

Journal Article Hypertension · June 1986 Components of the renin angiotensin system have been demonstrated in mouse and rat brains. However, local synthesis of renin has not been documented. In this study, we employed mouse submandibular gland renin complementary DNA (pDD-1D2) and rat liver angio ... Full text Link to item Cite

Acute thrombosis of a composite ascending aortic conduit containing a Bjork-Shiley valve during pregnancy: successful emergency cesarean section and operative repair.

Journal Article Clin Cardiol · June 1986 A 31-year-old female had an ascending aortic conduit with a Bjork-Shiley valve placed for an aortic dissection. A year later she became pregnant and was placed on heparin instead of coumadin therapy. She then developed a distal aortic dissection and was ho ... Full text Link to item Cite

Characterization of human prorenin expressed in mammalian cells from cloned cDNA.

Journal Article Proc Natl Acad Sci U S A · June 1986 Human preprorenin was synthesized in Chinese hamster ovary (CHO) cells transfected with an expression vector containing renin cDNA sequences. These cells secrete an inactive form of renin (EC 3.4.23.15) that can be activated by trypsin. This inactive renin ... Full text Link to item Cite

A monoclonal antibody specific for the amino terminal sequence of human prorenin identifies a common epitope on renal and amniotic fluid inactive renins.

Journal Article J Hypertens · June 1986 A synthetic nonapeptide corresponding to the predicted amino terminus of human prorenin was synthesized and used as an antigen in the production of mouse hybridomas. Forty-seven clones producing antibody to this peptide were identified and screened for abi ... Full text Link to item Cite

Adrenergic effects on plasma lipoprotein metabolism. Speculation on mechanisms of action.

Journal Article Am J Med · February 14, 1986 Recently, the effects of alpha-adrenergic and beta-adrenergic antagonists on plasma lipoprotein concentrations have been reported. Evidence from diverse lines of research has been brought together that suggests three potential mechanisms by which these ant ... Full text Link to item Cite

Monoclonal antibodies as molecular probes to study structural heterogeneity between human and animal renins and other aspartyl proteinases.

Journal Article J Clin Endocrinol Metab · February 1986 Monoclonal antibodies may be helpful in comparing the structural homology of renins of various animal species as well as other aspartyl proteinases. We obtained four hybridoma lines secreting monoclonal antibodies that inhibited 3 Goldblatt mU human renin ... Full text Link to item Cite

Regulation of tissue renin and angiotensin gene expressions.

Journal Article J Cardiovasc Pharmacol · 1986 Recent studies employing molecular biological techniques demonstrate that renin and angiotensinogen genes are expressed in various tissues. We have observed tissue-specific regulation of renin and angiotensinogen gene expressions. Renin expression in kidne ... Full text Link to item Cite

Cultured glomerular mesangial cells contain renin: influence of calcium and isoproterenol.

Journal Article J Cardiovasc Pharmacol · 1986 Glomerular mesangial cells are contractile cells responsive to a variety of vasoactive substances. In addition, they are capable of synthesizing prostaglandins and renin-like enzyme(s) (RLE). We examined the identity of the RLE in cultured rat mesangial ce ... Full text Link to item Cite

Dog inactive renin: biochemical characterization and secretion into renal plasma and lymph.

Journal Article Am J Physiol · January 1986 It has been suggested that the dog is a useful model for studies of inactive renin (IR). However, the nature and origin of the trypsin-activated angiotensin-forming activity in dog plasma have not been fully defined. We characterized dog IR using renin-spe ... Full text Link to item Cite

Multiple sites of regulation of mouse renin expression in ontogeny.

Journal Article Clin Exp Hypertens A · 1986 How local renin expression is regulated in many tissues has yet to be defined. In the present studies the ontogeny of renin in submandibular gland (SMG) and kidney of CD-1 mice was examined in order to determine whether renal and extrarenal renin are simil ... Full text Link to item Cite

Probing the renin active site by collisional quenching of endogenous fluorescence.

Journal Article J Biol Chem · December 5, 1985 The structural and enzymatic aspects of renin are of great interest in hypertension research. In this paper, we examine the solution accessibility of the three tryptophan (Trp) residues of mouse submaxillary gland renin by solute collisional fluorescence q ... Link to item Cite

Renin expression by vascular endothelial cells in culture.

Journal Article Circ Res · August 1985 Cultured bovine aortic endothelial cells were examined for renin activity by biochemical, immunological, and immunohistochemical techniques. When cell sonicates were incubated with renin substrate, linear generation of angiotensin I was observed (1.12 +/- ... Full text Link to item Cite

A cooperative multicenter study of captopril in congestive heart failure: hemodynamic effects and long-term response.

Journal Article Am Heart J · August 1985 The acute hemodynamic effects, long-term clinical efficacy, and safety of the oral angiotensin-converting enzyme inhibitor, captopril, were assessed in a multicenter cooperative study of 124 patients with heart failure resistant to digitalis and diuretics. ... Full text Link to item Cite

Pathophysiology of experimental renovascular hypertension.

Journal Article Am J Kidney Dis · April 1985 The genesis of renovascular hypertension follows a continuum from an acute to a chronic phase. Reduction in renal perfusion initiates renin release and angiotensin-mediated systemic vasoconstriction. Aldosterone secretion, sodium and water retention, and e ... Full text Link to item Cite

Nifedipine in severely hypertensive patients with congestive heart failure and preserved ventricular systolic function.

Journal Article Arch Intern Med · February 1985 Nifedipine was used successfully in nine patients with refractory hypertension and left ventricular hypertrophy who had symptoms of congestive heart failure despite preserved left ventricular systolic function. The administration of 10 or 20 mg of nifedipi ... Link to item Cite

In vivo inhibition of renin by antirenin antibodies: potential experimental and clinical applications.

Journal Article J Cardiovasc Pharmacol · 1985 The use of antirenin antibody and Fab may provide a more specific physiologic tool and potential therapeutic agent than the existing pharmacologic inhibitors. The antibody combining site, by virtue of its larger size than organic compounds, has the capacit ... Full text Link to item Cite

Hybridization studies with a renin cDNA probe: evidence for widespread expression of renin in the mouse.

Journal Article J Hypertens Suppl · December 1984 To delineate tissue sites of renin synthesis the levels of renin enzyme activity and renin mRNA sequence were measured in various organs of adult male outbred Swiss mice. Blots containing poly (A)+ RNA from each organ were hybridized to the renin cDNA prob ... Link to item Cite

Hyponatremia in congestive heart failure: implications for neurohumoral activation and responses to orthostasis.

Journal Article J Clin Endocrinol Metab · November 1984 To study the relationship between serum Na concentration and impairment of homeostatic mechanisms in advanced congestive heart failure (CHF), we evaluated the status of the sympathetic nervous system, renin-angiotensin system, and regional visceral blood f ... Full text Link to item Cite

Vascular wall renin-angiotensin pathway in control of the circulation. A hypothesis.

Journal Article Am J Med · October 5, 1984 Multiple lines of evidence support the existence of a vascular renin-angiotensin system independent of the circulating system. Vascular renin appears to originate from both uptake of plasma renin and in situ synthesis. Renin may bind to vascular endotheliu ... Full text Link to item Cite

Renal response to captopril in severe heart failure: role of furosemide in natriuresis and reversal of hyponatremia.

Journal Article Ann Intern Med · June 1984 To assess the effect of furosemide and captopril on renal function and hyponatremia in patients with severe heart failure, we studied two groups of patients with hyponatremia who were receiving digoxin therapy and whose sodium intake was 40 meq/d. One grou ... Full text Link to item Cite

Biochemical and immunological properties of dog brain isorenin.

Journal Article Endocrinology · June 1984 A neutral protease with angiotensin I-forming activity which could readily be separated from acid proteases and plasma and renal renin was obtained from extracts of dog brain. This enzyme has an apparent mol wt of 40,000 by Sephadex chromatography. On chro ... Full text Link to item Cite

Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation.

Journal Article Am J Physiol · March 1984 The use of antirenin antibody and its fragments as specific tools for the analysis of the role of renin in blood pressure regulation is assessed in this study. Specific immunoglobulin G (IgG) or its antibody fragments (Fab) raised against purified canine r ... Full text Link to item Cite

Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia.

Journal Article N Engl J Med · February 9, 1984 To determine whether prostaglandins are involved in circulatory homeostasis in congestive heart failure, we measured plasma levels of the metabolites of vasodilator prostaglandins I2 and E2 in 15 patients with severe chronic heart failure. Mean circulating ... Full text Link to item Cite

Granulocyte-angiotensin system. Identification of angiotensinogen as the plasma protein substrate of leukocyte cathepsin G.

Journal Article Biochemistry · January 17, 1984 Cathepsin G, a human lysosomal neutral protease, converts angiotensin I to angiotensin II and cleaves angiotensin II from a plasma protein substrate. Experiments were designed that identified and characterized cathepsin G substrate as human angiotensinogen ... Full text Link to item Cite

Hypertension: The evolution of a scientific journal

Journal Article Hypertension · January 1, 1984 Cite

Purification and characterization of one-chain and two-chain renins from mouse submandibular gland.

Journal Article Hypertension · 1984 Biosynthetic processing of mouse submandibular gland renin involved sequential proteolytic cleavages of preprorenin to prorenin; the prorenin, in turn, rapidly converted to one-chain and slowly to two-chain renins that were both enzymatically active. One-c ... Full text Link to item Cite

Comparison of renin-specific IgG and antibody fragments in studies of blood pressure regulation

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · January 1, 1984 The use of antirenin antibody and its fragments as specific tools for the analysis of the role of renin in blood pressure regulation is assessed in this study. Specific immunoglobulin G (IgG) or its antibody fragments (Fab) raised against purified canine r ... Cite

Influence of androgen on translatable renin mRNA in the mouse submandibular gland.

Journal Article Hypertension · 1984 In mature outbred Swiss male mice, submandibular gland renin enzyme activity is 4- and 10-fold higher than in glands of prepubescent males and mature females, respectively. Levels of translatable renin mRNA have been studied in mouse submandibular gland du ... Full text Link to item Cite

Monoclonal antibodies specific for human renin.

Journal Article Trans Assoc Am Physicians · 1984 Link to item Cite

Purification and characterization of one-chain and two-chain renins from mouse submandibular gland

Journal Article Hypertension · 1984 Biosynthetic processing of mouse submandibular gland renin involved sequential proteolytic cleavages of preprorenin to prorenin; the prorenin, in turn, rapidly converted to one-chain and slowly to two-chain renins that were both enzymatically active. One-c ... Cite

Vascular renin-angiotensin: a possible autocrine or paracrine system in control of vascular function.

Journal Article J Cardiovasc Pharmacol · 1984 Circulating angiotensin influences vascular tone via its receptors particularly at the precapillary vessels. In addition, an intrinsic renin-angiotensin system has been postulated to exist in vascular wall. In this study, we documented components of the re ... Link to item Cite

Vascular renin-angiotensin: A possible autocrine or paracrine system in control of vascular function

Journal Article Journal of Cardiovascular Pharmacology · January 1, 1984 Circulating angiotensin influences vascular tone via its receptors particularly at the precapillary vessels. In addition, an intrinsic renin-angiotensin system has been postulated to exist in vascular wall. In this study, we documented components of the re ... Cite

Isorenin in dog brain and other tissues.

Journal Article Clin Exp Hypertens A · 1984 Full text Link to item Cite

Neurohumoral mechanisms in heart failure: role in pathogenesis, therapy, and drug tolerance.

Journal Article Fed Proc · December 1983 Animal models of experimental heart failure have provided the basis of our current understanding of the role of the kidney and neurohumoral mechanisms in clinical congestive heart failure (CHF). The vasoconstrictor hormones, i.e., the renin-angiotensin sys ... Link to item Cite

Biosynthesis of renin: multiplicity of active and intermediate forms.

Journal Article Proc Natl Acad Sci U S A · November 1983 Processing of renin involves sequential proteolytic cleavages of a preproform to the active mature forms. Preprorenin is rapidly internalized cotranslationally into the rough endoplasmic reticulum and hydrolyzed by signal peptidase to produce prorenin. In ... Full text Link to item Cite

Symptomatic hypotension following the clonidine suppression test for pheochromocytoma.

Journal Article Arch Intern Med · November 1983 A 42-year-old man with generalized atherosclerosis underwent surgery of the left carotid artery with eventual placement of a Dacron graft bypassing the left carotid sinus. Subsequently, symptoms suggestive of pheochromocytoma developed, and 24-hour urine c ... Link to item Cite

Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics in two-kidney Goldblatt hypertension.

Journal Article Circ Res · November 1983 The renal microcirculation was assessed in non-clipped kidneys of 23 Munich-Wistar rats with two-kidney one-clip Goldblatt hypertension. Four weeks after placement of a renal arterial clip, mean systemic arterial pressure averaged 163 +/- 5 mm Hg in hypert ... Full text Link to item Cite

Captopril and renal insufficiency.

Journal Article N Engl J Med · September 15, 1983 Full text Link to item Cite

Immunoaffinity chromatography of canine high-molecular-weight renin: partial purification and characterization.

Journal Article Clin Sci (Lond) · August 1983 Canine high-molecular-weight renin (mol. wt. 60 000) is believed to be a complex of renin (low-molecular-weight form, mol. wt. 40 000) and renin-binding substance. The immunocross-reactivity of high-molecular-weight renin and low-molecular-weight renin was ... Full text Link to item Cite

Compensatory response to hemorrhage in conscious dogs on normal and low salt intake.

Journal Article Am J Physiol · March 1983 The compensatory response to moderately severe hemorrhage (30 ml/kg) was studied in chronically catheterized conscious dogs maintained on normal and low salt intake. Although the fall in blood pressure and the increase in heart rate were similar in the two ... Full text Link to item Cite

The feedback regulation of angiotensinogen production by components of the renin-angiotensin system.

Journal Article Circ Res · March 1983 The in vivo generation of angiotensin appears to be dependent on both plasma renin and angiotensinogen concentrations. Much less is known about the control of hepatic angiotensinogen synthesis and release, as compared to that of renin. In this study, we ex ... Full text Link to item Cite

Characterization of inactive renin from human kidney and plasma. Evidence of a renal source of circulating inactive renin.

Journal Article J Clin Invest · March 1983 An inactive form of renin has been isolated from human plasma. It has been suggested that this may represent renin precursor secreted from the kidney. However, early studies failed to isolate inactive renin from human renal tissue. In this investigation, r ... Full text Link to item Cite

Is renin a factor in the etiology of essential hypertension?

Journal Article Hypertension · 1983 The widespread clinical study of converting-enzyme inhibitors has shown that they are effective antihypertensive drugs even in patients who may manifest either normal or decreased plasma renin activity. This suggests either that renin in a site other than ... Full text Link to item Cite

Compensatory response to hemorrhage in conscious dogs on normal and low salt intake

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · January 1, 1983 The compensatory response to moderately severe hemorrhage (30 ml/kg) was studied in chronically catheterized conscious dogs maintained on normal and low salt intake. Although the fall in blood pressure and the increase in heart rate were similar in the two ... Cite

Effect of intrarenal administration of dopamine on renin release in conscious dogs.

Journal Article Am J Physiol · January 1983 We investigated the effect of intrarenal administration of dopamine on renin release in conscious dogs. Dopamine in doses ranging from 0.28 to 3.0 micrograms . kg(-1) . min(-1) produced a significant increase in systemic plasma renin activity (PRA) and ren ... Full text Link to item Cite

Effect of intrarenal administration of dopamine on renin release in conscious dogs

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · January 1, 1983 We investigated the effect of intrarenal administration of dopamine on renin release in conscious dogs. Dopamine in doses ranging from 0.28 to 3.0 μg·kg -1 ·min -1 produced a significant increase in systemic plasma renin activity (PRA) and renin secretion ... Cite

Antibodies as specific renin inhibitors: studies with polyclonal and monoclonal antibodies and Fab fragments.

Journal Article Clin Exp Hypertens A · 1983 The use of antirenin antibody and Fab may provide a more specific physiologic tool and potential therapeutic agent than the existing pharmacologic inhibitors. The antibody combining site, by virtue of its larger size than organic compounds, has the capacit ... Full text Link to item Cite

Is renin a factor in the etiology of essential hypertension?

Journal Article Hypertension · 1983 The widespread clinical study of converting-enzyme inhibitors has shown that they are effective antihypertensive drugs even in patients who may manifest either normal or decreased plasma renin activity. This suggests either that renin in a site other than ... Cite

Evidence for renin in rat brain: differentiation from other reninlike enzymes.

Journal Article Am J Physiol · May 1982 We observed that unfractionated rat brain extract incubated with substrate at pH 6.0 yielded 12 times the quantity of angiotensin I as incubations at pH 7.4, but the enzyme activity measured at pH 6 was not primarily due to renin. To examine the existence ... Full text Link to item Cite

Hormonal control of angiotensinogen production.

Journal Article Life Sci · February 15, 1982 The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was us ... Full text Link to item Cite

Renin synthesis by canine aortic smooth muscle cells in culture.

Journal Article Life Sci · January 4, 1982 Angiotensin-I generating activity has been detected in homogenates of arterial tissue but it remains unclear whether this enzymatic activity results from the presence of renin itself or from the action of other proteases such as cathepsin D. In an assay sy ... Full text Link to item Cite

The nature of renin precursor and inactive renin.

Journal Article Clin Exp Hypertens A · 1982 The biosynthesis of renin in the mouse submaxillary gland was defined using both cell-free translation and pulse-labelling methods. Renin is synthesized as a preproform and cleaved by microsomes to the proform. Prorenin (MW = 46 kilodaltons, pI 6.35) is pr ... Full text Link to item Cite

Evidence for renin in rat brain: Differentiation from other reninlike enzymes

Journal Article American Journal of Physiology - Endocrinology and Metabolism · January 1, 1982 We observed that unfractionated rat brain extract incubated with substrate at pH 6.0 yieded 12 times the quantity of angiotensin I as incubations at pH 7.4, due to renin. To examine the existence of renin in brain, we used three methods of affinity chromat ... Cite

Characterization of antibodies to canine renal renin. Studies of interspecies homology of renin using antibodies as probe.

Journal Article Hypertension · 1982 Antibodies raised to pure canine renal renin were used to probe homology of renin from other species. Goat, rabbit, and mouse antibodies exhibited similar properties and were specific for renin as confirmed by immunodiffusion, immunoelectrophoresis, and se ... Full text Link to item Cite

The regulation of angiotensinogen biosynthesis by the pituitary gland

Journal Article Federation Proceedings · January 1, 1982 Cite

Isolation and regulation of brain renin

Journal Article Experimental Brain Research · January 1, 1982 Full text Cite

Regulation of brain renin: Evidence for an independent brain renin

Journal Article Clinical Science · January 1, 1982 Cite

Prevalence of abnormal thyroid function test results in patients with acute medical illnesses.

Journal Article Am J Med · January 1982 We measured serum total and free thyroxine (T4) and triiodothyronine (T3) concentrations, free T4 and T3 indexes, thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) concentrations in 98 patients hosp ... Full text Link to item Cite

Studies of the biosynthesis of renin with a cell-free translation system.

Journal Article Clin Sci (Lond) · December 1981 1. Poly(A)+ mRNA from mouse submaxillary gland encodes a polypeptide of molecular weight 48 000 (48K polypeptide) which is abundant in the male. 2. This polypeptide is selectively absent in the translation products of mRNA from a strain of genetically reni ... Full text Link to item Cite

Abundant androgen regulated mRNAs in mouse submandibular gland: cell-free translation of renin precursor mRNA.

Journal Article Nucleic Acids Res · July 24, 1981 Submandibular glands of male mice contain at least four abundant mRNAs that occur at low concentrations in glands of females. The male-specific mRNAs code for polypeptides of 48,000, 43,000, 29,000, and 27,000 MW. Androgenic regulation of these mRNAs is il ... Full text Link to item Cite

Monoclonal antibodies binding renal renin.

Journal Article Hypertension · 1981 Somatic-cell fusion of normal antibody-producing spleen cells with cells from a plasmacytoma culture results in a culture of hybrid cells from which a monoclonal line may be selected. These lines are immortal and may be amplified as tumors in syngeneic ani ... Full text Link to item Cite

Sequential renal hemodynamics in experimental benign and malignant hypertension.

Journal Article Hypertension · 1981 To examine the sequential renal hemodynamic changes in experimental renovascular hypertension, the uninephrectomized dog was studied immediately after renal artery constriction, throughout chronic benign hypertension, and during malignant hypertension. Int ... Full text Link to item Cite

The possible role of dopamine in the regulation of renin release

Journal Article Physiologist · January 1, 1981 Cite

Monoclonal antibodies binding renal renin

Journal Article Hypertension · 1981 somatic-cell fusion of normal antibody-producing spleen cells with cells from a plasmacytoma culture results in a culture of hybrid cells from which a monoclonal line may be selected. These lines are immortal and may be amplified as tumors in syngeneic ani ... Cite

A trial of two strategies to modify the test-ordering behavior of medical residents.

Journal Article N Engl J Med · December 4, 1980 We studied two methods to reduce the ordering of laboratory and radiologic tests by medical residents in their first postgraduate year. Dividing the residents into three groups, we compared the effect of concurrent chart review and discussion in one group ... Full text Link to item Cite

Identification of renin and renin-like enzymes in rat brain by a renin-specific antibody.

Journal Article Clin Sci (Lond) · December 1980 1. The major angiotensin I-generating activity of rat brain extracts has a pH optimum different from that of renal renin and is not inhibited by renin specific antibody. 2. Affinity chromatography utilizing renin specific antibody, pepstatin and alpha-case ... Full text Link to item Cite

Are uncontrolled clinical studies ever justified?

Journal Article N Engl J Med · October 30, 1980 Full text Link to item Cite

Sustained effectiveness of converting-enzyme inhibition in patients with severe congestive heart failure.

Journal Article N Engl J Med · June 19, 1980 Eight patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were given captopril (seven patients) or teprotide (one patient). All had dyspnea, edema, elevated pulmonary wedge pressure (28.0 +/- 2.6 mm Hg) ... Full text Link to item Cite

Renin-specific antibody for study of cardiovascular homeostasis.

Journal Article Science · March 7, 1980 Antiserum specific for purified canine renal renin was used to inhibit this enzyme in trained, conscious dogs. The antiserum did not affect blood pressure in sodium-replete dogs but decreased plasma renin activity and blood pressure in sodium-depleted anim ... Full text Link to item Cite

Complete purification of dog renal renin.

Journal Article Biochemistry · November 13, 1979 Full text Link to item Cite

Purification of human renal renin.

Journal Article Clin Sci Mol Med Suppl · December 1978 1. Human renal renin has been purified 200 000-fold from cadaver kidney cortex by a method which employs affinity chromatography on aminohexyl peptstatin. 2. The product of this purification has a specific activity of 400 Goldblatt units/mg when compared w ... Full text Link to item Cite

Pure dog renal renin

Journal Article Circulation · January 1, 1978 Cite

Complete purification of human renin

Journal Article Circulation · January 1, 1978 Cite

Intrarenal dopaminergic receptors in control of renin release in the conscious dog

Journal Article Federation Proceedings · January 1, 1978 Cite

Aspiration of metallic mercury. A 22-year follow-up.

Journal Article JAMA · October 3, 1977 Rupture of the mercury-filled bag of an intestinal tube resulted in aspiration of metallic mercury 22 years ago in the patient reported. Immediate respiratory distress was treated with vigorous suctioning and postural drainage. Follow-up chest roentgenogra ... Link to item Cite

Pathogenesis of duodenal ulcer. Gastric hyperacidity caused by propionitrile and cysteamine in rats.

Journal Article Res Commun Chem Pathol Pharmacol · February 1977 Cysteamine and propionitrile, experimental duodenal ulcerogens, stimulated gastric acid secretion in the rat. Gastric acid secretion was measured by two separate methods, the conventional pylorus ligation technique and a non-invasive technique based on the ... Link to item Cite

Effect of vinblastine on rat liver ultrastructure.

Journal Article Arzneimittelforschung · 1977 A single injection of vinblastine given i.v. to rats lead to the disappearance of microtubules, development of crystalline inclusions, dilation of Golgi sacculi, formation of multivesicular bodies and cytosegresomes as well as accumulation of lysosomes in ... Link to item Cite

Vibrio fetus endocarditis in a patient with systemic lupus erythematosus.

Journal Article Am J Med Sci · 1976 Vibrio fetus endocarditis occurred in a patient with systemic lupus erythematosus receiving azathoprin and prednisone. Blood cultures required 14 days to become positive. The fastidious growth requirement of this organism is reviewed because lack of apprec ... Full text Link to item Cite

Letter: Hepatic bridging--a semantic collapse.

Journal Article N Engl J Med · July 25, 1974 Link to item Cite

Effect of propionitrile and cysteamine on gastric secretion in rats

Journal Article Clinical Research · January 1, 1974 Cite