Scholars@Duke
Yibin Wang

Yibin Wang

Professor in Medicine
Medicine, Cardiology

Selected Publications

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Journal Article Sci Rep · September 5, 2024 Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac d ... Full text Link to item Cite

Brain-Targeted Cas12a Ribonucleoprotein Nanocapsules Enable Synergetic Gene Co-Editing Leading to Potent Inhibition of Orthotopic Glioblastoma.

Journal Article Adv Sci (Weinh) · September 2024 Gene-editing technology shows great potential in glioblastoma (GBM) therapy. Due to the complexity of GBM pathogenesis, a single gene-editing-based therapy is unlikely to be successful; therefore, a multi-gene knockout strategy is preferred for effective G ... Full text Link to item Cite

Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction.

Journal Article Circ Res · August 16, 2024 BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabol ... Full text Link to item Cite

Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection.

Journal Article Apoptosis · August 2024 In SARS-CoV-2 infection, it has been observed that viral replication lasts longer in the nasal mucosa than in the lungs, despite the presence of a high viral load at both sites. In hamsters, we found that the nasal mucosa exhibited a mild inflammatory resp ... Full text Link to item Cite

The potential mechanisms and treatment effects of stem cell-derived exosomes in cardiac reengineering.

Journal Article Nanotechnology · June 20, 2024 Exosomes are extracellular vesicles of diverse compositions that are secreted by numerous cell types. Exosomes contain significant bioactive components, including lipids, proteins, mRNA, and miRNA. Exosomes play an important role in regulating cellular sig ... Full text Link to item Cite

Effectiveness and safety of PD-1/PD-L1 inhibitors monotherapy in patients with endometrial cancer.

Journal Article Discov Oncol · May 15, 2024 BACKGROUND: Studies evaluating the effectiveness of immune checkpoint inhibitors (ICI) for endometrial cancer (EC) are limited. This study aimed to assess the efficacy of PD-1/PD-L1 inhibitors as monotherapy for EC by conducting a meta-analysis. The predic ... Full text Link to item Cite

Impact of Aging on Cardiovascular Diseases: From Chronological Observation to Biological Insights: JACC Family Series.

Journal Article JACC Asia · May 2024 Cardiovascular disease (CVD) has increasing challenges for human health with an increasingly aging population worldwide, imposing a significant obstacle to the goal of healthy aging. Rapid advancements in our understanding of biological aging process have ... Full text Link to item Cite

Swarm Autonomy: From Agent Functionalization to Machine Intelligence.

Journal Article Adv Mater · April 23, 2024 Swarm behaviors are common in nature, where individual organisms collaborate via perception, communication, and adaptation. Emulating these dynamics, large groups of active agents can self-organize through localized interactions, giving rise to complex swa ... Full text Link to item Cite

The BCKDK inhibitor BT2 is a chemical uncoupler that lowers mitochondrial ROS production and de novo lipogenesis.

Journal Article J Biol Chem · March 2024 Elevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoaci ... Full text Link to item Cite

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Journal Article Sci Transl Med · February 14, 2024 Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains i ... Full text Link to item Cite

The Role of Branched-chain Amino Acids and Their Metabolism in Cardiovascular Diseases.

Journal Article J Cardiovasc Transl Res · February 2024 Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for protein synthesis. Recent studies have yielded new insights into their diverse physiological and pathological roles in health and disease. Cardiova ... Full text Link to item Cite

Branched-chain amino acids promote hepatic Cyp7a1 expression and bile acid synthesis via suppressing FGF21-ERK pathway

Journal Article Acta Pharmacologica Sinica · January 1, 2024 Branched-chain amino acids (BCAAs) including leucine, isoleucine and valine have been linked with metabolic and cardiovascular diseases. BCAAs homeostasis is tightly controlled by their catabolic pathway. BCKA dehydrogenase (BCKD) complex is the rate-limit ... Full text Cite

The East Asian wild apples, Malus baccata (L.) Borkh and Malus hupehensis (Pamp.) Rehder., are additional contributors to the genomes of cultivated European and Chinese varieties.

Journal Article Mol Ecol · September 2023 The domestication process in long-lived plant perennials differs dramatically from that of annuals, with a huge amount of genetic exchange between crop and wild populations. Though apple is a major fruit crop grown worldwide, the contribution of wild apple ... Full text Link to item Cite

Regulated cell death pathways in cardiomyopathy.

Journal Article Acta Pharmacol Sin · August 2023 Heart disease is a worldwide health menace. Both intractable primary and secondary cardiomyopathies contribute to malignant cardiac dysfunction and mortality. One of the key cellular processes associated with cardiomyopathy is cardiomyocyte death. Cardiomy ... Full text Link to item Cite

Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.

Journal Article Acta Pharmacol Sin · July 2023 Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target for heart failure. However, BCAA catabolic enzymes are u ... Full text Link to item Cite

Branched-chain keto acids inhibit mitochondrial pyruvate carrier and suppress gluconeogenesis in hepatocytes.

Journal Article Cell Rep · June 27, 2023 Branched-chain amino acid (BCAA) metabolism is linked to glucose homeostasis, but the underlying signaling mechanisms are unclear. We find that gluconeogenesis is reduced in mice deficient of Ppm1k, a positive regulator of BCAA catabolism, which protects a ... Full text Link to item Cite

Rtf1 Transcriptionally Regulates Neonatal and Adult Cardiomyocyte Biology.

Journal Article J Cardiovasc Dev Dis · May 20, 2023 The PAF1 complex component Rtf1 is an RNA Polymerase II-interacting transcription regulatory protein that promotes transcription elongation and the co-transcriptional monoubiquitination of histone 2B. Rtf1 plays an essential role in the specification of ca ... Full text Link to item Cite

Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction.

Journal Article Cardiovasc Res · May 2, 2023 AIMS: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeut ... Full text Link to item Cite

Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

Journal Article Circulation. Cardiovascular quality and outcomes · April 2023 BackgroundThe double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarct ... Full text Cite

The global burden of metabolic disease: Data from 2000 to 2019.

Journal Article Cell Metab · March 7, 2023 Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoho ... Full text Link to item Cite

A two-decade population-based study on the effect of hypertension in the general population with obesity in the United States.

Journal Article Obesity (Silver Spring) · March 2023 OBJECTIVE: With rising prevalence of hypertension and obesity, the effect of hypertension in obesity remains an important global issue. The prognosis of the US general population with obesity based on hypertension control was examined. METHODS: This study ... Full text Link to item Cite

Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure

Journal Article Frontiers in Cardiovascular Medicine · January 1, 2023 Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabete ... Full text Cite

Metabolic and senescence characteristics associated with the immune microenvironment in ovarian cancer.

Journal Article Front Endocrinol (Lausanne) · 2023 Ovarian cancer is a highly malignant gynecological cancer influenced by the immune microenvironment, metabolic reprogramming, and cellular senescence. This review provides a comprehensive overview of these characteristics. Metabolic reprogramming affects i ... Full text Link to item Cite

A novel murine model of atrial fibrillation by diphtheria toxin-induced injury

Journal Article Frontiers in Physiology · October 31, 2022 The treatment of atrial fibrillation (AF) continues to be a significant clinical challenge. While genome-wide association studies (GWAS) are beginning to identify AF susceptibility genes (Gudbjartsson et al., Nature, 2007, 448, 353–357; Choi et al., Circ. ... Full text Cite

LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.

Journal Article Circ Res · October 14, 2022 RATIONALE: Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polyp ... Full text Link to item Cite

Lipid-independent activation of a muscle-specific PKCα splicing variant.

Journal Article Am J Physiol Heart Circ Physiol · October 1, 2022 Protein kinase C-α (PKCα) plays a major role in a diverse range of cellular processes. Studies to date have defined the regulatory controls and function of PKCα entirely based upon the previously annotated ubiquitously expressed prototypical isoform. From ... Full text Link to item Cite

Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis.

Journal Article Circ Res · July 5, 2022 BACKGROUND: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) a ... Full text Link to item Cite

Sex differences in heart mitochondria regulate diastolic dysfunction.

Journal Article Nat Commun · July 4, 2022 Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial sex differences might underlie this bias. As part of genetic studies of heart failure in mice, we observe ... Full text Link to item Cite

YAP: The nexus between metabolism and cardiac remodeling.

Journal Article J Clin Invest · March 15, 2022 Cardiomyocyte hypertrophy is an integral part of cardiac remodeling that occurs under physiological or pathological stresses. It can lead to heart failure in a pathological form or oppose functional deterioration in a compensatory one. The mechanisms under ... Full text Link to item Cite

Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

Journal Article Circ Res · March 4, 2022 BACKGROUND: Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle ene ... Full text Link to item Cite

Circular RNA circEsyt2 regulates vascular smooth muscle cell remodeling via splicing regulation.

Journal Article J Clin Invest · December 15, 2021 Circular RNAs (circRNAs) have been recently recognized as playing a role in the pathogenesis of vascular remodeling-related diseases by modulating the functions of miRNAs. However, the interplay between circRNAs and proteins during vascular remodeling rema ... Full text Link to item Cite

A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques.

Journal Article Sci Transl Med · December 15, 2021 Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and has become a leading indication for liver transplantation in the United States. The development of effective therapies for NASH is a major unmet need. Here, we identified a small molecu ... Full text Link to item Cite

Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.

Journal Article Sci Transl Med · December 15, 2021 Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landsc ... Full text Link to item Cite

Triiodothyronine and dexamethasone alter potassium channel expression and promote electrophysiological maturation of human-induced pluripotent stem cell-derived cardiomyocytes.

Journal Article J Mol Cell Cardiol · December 2021 BACKGROUND: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising tool for disease modeling and drug development. However, hiPSC-CMs remain functionally immature, which hinders their utility as a model of human ... Full text Link to item Cite

Aging Affects KV7 Channels and Perivascular Adipose Tissue-Mediated Vascular Tone

Journal Article Frontiers in Physiology · November 26, 2021 Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and dow ... Full text Cite

Loss of Endothelial Hypoxia Inducible Factor-Prolyl Hydroxylase 2 Induces Cardiac Hypertrophy and Fibrosis.

Journal Article J Am Heart Assoc · November 16, 2021 Background Cardiac hypertrophy and fibrosis are common adaptive responses to injury and stress, eventually leading to heart failure. Hypoxia signaling is important to the (patho)physiological process of cardiac remodeling. However, the role of endothelial ... Full text Link to item Cite

Early adaptive chromatin remodeling events precede pathologic phenotypes and are reinforced in the failing heart.

Journal Article J Mol Cell Cardiol · November 2021 The temporal nature of chromatin structural changes underpinning pathologic transcription are poorly understood. We measured chromatin accessibility and DNA methylation to study the contribution of chromatin remodeling at different stages of cardiac hypert ... Full text Link to item Cite

Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species.

Journal Article Cell Metab · October 5, 2021 Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals be ... Full text Link to item Cite

The coming of age for branched-chain amino acids

Journal Article Journal of Cardiovascular Aging · October 1, 2021 Full text Cite

Editors’ Preamble to The Journal of Cardiovascular Aging

Journal Article Journal of Cardiovascular Aging · October 1, 2021 Full text Cite

Metal dependent protein phosphatase PPM family in cardiac health and diseases.

Journal Article Cell Signal · September 2021 Protein phosphorylation and dephosphorylation is central to signal transduction in nearly every aspect of cellular function, including cardiovascular regulation and diseases. While protein kinases are often regarded as the molecular drivers in cellular sig ... Full text Link to item Cite

mTOR Activation Initiates Renal Cell Carcinoma Development by Coordinating ERK and p38MAPK.

Journal Article Cancer Res · June 15, 2021 Renal cell carcinoma (RCC) mainly originates from renal proximal tubules. Intriguingly, disruption of genes frequently mutated in human RCC samples thus far has only generated RCC originated from other renal tubule parts in mouse models. This hampers our u ... Full text Link to item Cite

A risk score based on baseline risk factors for predicting mortality in COVID-19 patients.

Journal Article Curr Med Res Opin · June 2021 BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medic ... Full text Link to item Cite

Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure.

Journal Article JCI Insight · May 24, 2021 Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly ... Full text Link to item Cite

Development and validation of a risk score using complete blood count to predict in-hospital mortality in COVID-19 patients.

Journal Article Med · April 9, 2021 BACKGROUND: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). METHODS: We performed a retrospective cohort study from a total of 13,138 inpatients with ... Full text Link to item Cite

The right ventricular transcriptome signature in Ossabaw swine with cardiometabolic heart failure: implications for the coronary vasculature.

Journal Article Physiol Genomics · March 1, 2021 Heart failure (HF) patients with deteriorating right ventricular (RV) structure and function have a nearly twofold increased risk of death compared with those without. Despite the well-established clinical risk, few studies have examined the molecular sign ... Full text Link to item Cite

Cardioprotective Effect of Anesthetics: Translating Science to Practice.

Journal Article J Cardiothorac Vasc Anesth · March 2021 Cardiovascular diseases are the number one cause of mortality in the world, particularly among the aging population. Major adverse cardiac events are also a major contributor to perioperative complications, affecting 2.6% of noncardiac surgeries and up to ... Full text Link to item Cite

The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19.

Journal Article Cell Metab · February 2, 2021 Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospital ... Full text Link to item Cite

Kidney Function Indicators Predict Adverse Outcomes of COVID-19.

Journal Article Med · January 15, 2021 BACKGROUND: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis ... Full text Link to item Cite

MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes.

Journal Article J Mol Cell Cardiol · November 2020 The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a public health emergency of international concern as more than 15 million cases were reported by 24th July 2020. Angiotensin-converting enzyme 2 (ACE2) is a COVID-19 entry ... Full text Link to item Cite

The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation.

Journal Article Cell Rep · October 13, 2020 Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. ... Full text Link to item Cite

Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes.

Journal Article Cell Metab · October 6, 2020 The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescrib ... Full text Link to item Cite

Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19.

Journal Article Hypertension · October 2020 The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed ... Full text Link to item Cite

Tribute to Dr. Steve Schwartz.

Journal Article J Mol Cell Cardiol · October 2020 Full text Link to item Cite

p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart.

Journal Article J Clin Invest · October 1, 2020 In the mammalian heart, the left ventricle (LV) rapidly becomes more dominant in size and function over the right ventricle (RV) after birth. The molecular regulators responsible for this chamber-specific differential growth are largely unknown. We found t ... Full text Link to item Cite

Mitochondrial CaMKII causes adverse metabolic reprogramming and dilated cardiomyopathy.

Journal Article Nat Commun · September 4, 2020 Despite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. Here, we report increased mitocho ... Full text Link to item Cite

Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.

Journal Article Cell · August 6, 2020 Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart ... Full text Link to item Cite

In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19.

Journal Article Cell Metab · August 4, 2020 Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a ... Full text Link to item Cite

Systems Genetics for Mechanistic Discovery in Heart Diseases.

Journal Article Circ Res · June 5, 2020 Cardiovascular diseases are the leading cause of death worldwide. Complex diseases with highly heterogenous disease progression among patient populations, cardiovascular diseases feature multifactorial contributions from both genetic and environmental stre ... Full text Link to item Cite

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

Journal Article Circ Res · June 5, 2020 RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the associa ... Full text Link to item Cite

Low-Dose Sorafenib Acts as a Mitochondrial Uncoupler and Ameliorates Nonalcoholic Steatohepatitis.

Journal Article Cell Metab · May 5, 2020 Nonalcoholic steatohepatitis (NASH) is becoming one of the leading causes of hepatocellular carcinoma (HCC). Sorafenib is the only first-line therapy for advanced HCC despite its serious adverse effects. Here, we report that at an equivalent of approximate ... Full text Link to item Cite

mRNA Metabolism in Cardiac Development and Disease: Life After Transcription.

Journal Article Physiol Rev · April 1, 2020 The central dogma of molecular biology illustrates the importance of mRNAs as critical mediators between genetic information encoded at the DNA level and proteomes/metabolomes that determine the diverse functional outcome at the cellular and organ levels. ... Full text Link to item Cite

Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway.

Journal Article Nat Commun · January 2, 2020 Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regula ... Full text Link to item Cite

Gene-environment regulatory circuits of right ventricular pathology in tetralogy of fallot.

Journal Article J Mol Med (Berl) · December 2019 The phenotypic spectrum of congenital heart defects (CHDs) is contributed by both genetic and environmental factors. Their interactions are profoundly heterogeneous but may operate on common pathways as in the case of hypoxia signaling during postnatal hea ... Full text Link to item Cite

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice.

Journal Article J Vis Exp · October 3, 2019 Isoproterenol (ISO), is a non-selective beta-adrenergic agonist, that is used widely to induce cardiac injury in mice. While the acute model mimics stress-induced cardiomyopathy, the chronic model, administered through an osmotic pump, mimics advanced hear ... Full text Link to item Cite

BCAA Catabolic Defect Alters Glucose Metabolism in Lean Mice

Journal Article Frontiers in Physiology · September 4, 2019 Recent studies show branched-chain amino acid (BCAA) catabolic pathway is defective in obese animals and humans, contributing to the pathogenesis of insulin resistance and diabetes. However, in the context of obesity, various processes including the dysfun ... Full text Cite

A new branch connecting thermogenesis and diabetes.

Journal Article Nat Metab · September 2019 Systemic accumulation of branched-chain amino acids (BCAAs) is a major metabolic hallmark and contributor to insulin resistance associated with obesity. A recent report identifies SLC25A44 as the BCAA transporter in mitochondrial membranes and shows that B ... Full text Link to item Cite

Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance.

Journal Article Diabetes · September 2019 Recent studies implicate a strong association between elevated plasma branched-chain amino acids (BCAAs) and insulin resistance (IR). However, a causal relationship and whether interrupted BCAA homeostasis can serve as a therapeutic target for diabetes rem ... Full text Link to item Cite

Isoproterenol-Induced Cardiac Diastolic Dysfunction in Mice: A Systems Genetics Analysis

Journal Article Frontiers in Cardiovascular Medicine · July 31, 2019 We examined an isoproterenol heart failure model across a panel of diverse inbred strains of mice, the Hybrid Mouse Diversity Panel (HMDP), using left atrial (LA) and lung weights as well as echocardiogram parameters as surrogates for cardiac diastolic fun ... Full text Cite

Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.

Journal Article J Am Heart Assoc · June 4, 2019 Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods ... Full text Link to item Cite

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

Journal Article JACC Basic Transl Sci · June 2019 The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Os ... Full text Link to item Cite

Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study.

Journal Article Am J Clin Nutr · June 1, 2019 BACKGROUND: Recent studies have shown that circulating branched-chain amino acids (BCAAs) are elevated in obese, insulin-resistant individuals. However, it is not known if supplementation of additional BCAAs will further impair glucose metabolism. OBJECTIV ... Full text Link to item Cite

Epigenetics in dilated cardiomyopathy.

Journal Article Curr Opin Cardiol · May 2019 PURPOSE OF REVIEW: Characterized by enlarged ventricle and loss of systolic function, dilated cardiomyopathy (DCM) has the highest morbidity among all the cardiomyopathies. Although it is well established that DCM is typically caused by mutations in a larg ... Full text Link to item Cite

WIPI1 is a conserved mediator of right ventricular failure.

Journal Article JCI Insight · April 25, 2019 Right ventricular dysfunction is highly prevalent across cardiopulmonary diseases and independently predicts death in both heart failure (HF) and pulmonary hypertension (PH). Progression towards right ventricular failure (RVF) can occur in spite of optimal ... Full text Link to item Cite

Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

Journal Article JACC Basic Transl Sci · April 2019 Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfun ... Full text Link to item Cite

RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure.

Journal Article Proc Natl Acad Sci U S A · March 26, 2019 Heart performance relies on highly coordinated excitation-contraction (EC) coupling, and defects in this critical process may be exacerbated by additional genetic defects and/or environmental insults to cause eventual heart failure. Here we report a regula ... Full text Link to item Cite

Direct visualization of cardiac transcription factories reveals regulatory principles of nuclear architecture during pathological remodeling.

Journal Article J Mol Cell Cardiol · March 2019 Heart failure is associated with hypertrophying of cardiomyocytes and changes in transcriptional activity. Studies from rapidly dividing cells in culture have suggested that transcription may be compartmentalized into factories within the nucleus, but this ... Full text Link to item Cite

Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure.

Journal Article Circ Res · January 4, 2019 On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium, Cardiovascular Bioengineering Symposium, was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance t ... Full text Link to item Cite

Systems Genetics Approach to Biomarker Discovery: GPNMB and Heart Failure in Mice and Humans.

Journal Article G3 (Bethesda) · November 6, 2018 We describe a simple bioinformatics method for biomarker discovery that is based on the analysis of global transcript levels in a population of inbred mouse strains showing variation for disease-related traits. This method has advantages such as controlled ... Full text Link to item Cite

Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac Fibrosis.

Journal Article Circulation · September 18, 2018 BACKGROUND: Genetic diversity and the heterogeneous nature of cardiac fibroblasts (CFbs) have hindered characterization of the molecular mechanisms that regulate cardiac fibrosis. The Hybrid Mouse Diversity Panel offers a valuable tool to examine genetical ... Full text Link to item Cite

Humanin analog enhances the protective effect of dexrazoxane against doxorubicin-induced cardiotoxicity.

Journal Article Am J Physiol Heart Circ Physiol · September 1, 2018 The chemotherapeutic effect of doxorubicin (Dox) is limited by cumulative dose-dependent cardiotoxicity in cancer survivors. Dexrazoxane (DRZ) is approved to prevent Dox-induced cardiotoxicity. Humanin and its synthetic analog HNG have a cytoprotective eff ... Full text Link to item Cite

Identification and Characterization of miRNAs in Self-Rooted and Grafted Malus Reveals Critical Networks Associated with Flowering.

Journal Article Int J Mol Sci · August 13, 2018 Grafting can improve the agricultural traits of crop plants, especially fruit trees. However, the regulatory networks and differentially expressed microRNAs (miRNAs) related to grafting in apple remain unclear. Herein, we conducted high-throughput sequenci ... Full text Link to item Cite

Genome-wide identification, characterization and expression analysis of long non-coding RNAs in different tissues of apple.

Journal Article Gene · August 5, 2018 Recently, the long non-coding RNAs (lncRNAs), which play important roles in various complex biological processes, have received more attention in plants. However, little information is available on lncRNAs in woody fruit trees and their potential regulator ... Full text Link to item Cite

The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure.

Journal Article J Biol Chem · June 22, 2018 Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce ... Full text Link to item Cite

EZH2 RIP-seq Identifies Tissue-specific Long Non-coding RNAs.

Journal Article Curr Gene Ther · 2018 BACKGROUND: Polycomb Repressive Complex 2 (PRC2) catalyzes histone methylation at H3 Lys27, and plays crucial roles during development and diseases in numerous systems. Its catalytic subunit EZH2 represents a key nuclear target for long non-coding RNAs (ln ... Full text Link to item Cite

Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture.

Journal Article F1000Res · 2018 Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis ... Full text Link to item Cite

A personalized, multiomics approach identifies genes involved in cardiac hypertrophy and heart failure.

Journal Article NPJ Syst Biol Appl · 2018 A traditional approach to investigate the genetic basis of complex diseases is to identify genes with a global change in expression between diseased and healthy individuals. However, population heterogeneity may undermine the effort to uncover genes with s ... Full text Link to item Cite

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

Journal Article Circulation · October 24, 2017 BACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. METHODS: To investigate the mechanisms of epigenomic function in the heart, gen ... Full text Link to item Cite

Wnt11 regulates cardiac chamber development and disease during perinatal maturation.

Journal Article JCI Insight · September 7, 2017 Ventricular chamber growth and development during perinatal circulatory transition is critical for functional adaptation of the heart. However, the chamber-specific programs of neonatal heart growth are poorly understood. We used integrated systems genomic ... Full text Link to item Cite

Untangle a Broken Heart via Janus Kinase 1.

Journal Article Circ Res · September 1, 2017 Full text Link to item Cite

The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes.

Journal Article Elife · August 19, 2017 Altered Ca2+ handling is often present in diseased hearts undergoing structural remodeling and functional deterioration. However, whether Ca2+ directly regulates sarcomere structure has remained elusive. Using a zebrafish ncx1 mutant, we explored the impac ... Full text Link to item Cite

Cardiac myocyte p38α kinase regulates angiogenesis via myocyte-endothelial cell cross-talk during stress-induced remodeling in the heart.

Journal Article J Biol Chem · August 4, 2017 Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptos ... Full text Link to item Cite

p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner.

Journal Article Sci Rep · April 6, 2017 Bone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are acti ... Full text Link to item Cite

A systems genetics approach identifies Trp53inp2 as a link between cardiomyocyte glucose utilization and hypertrophic response.

Journal Article Am J Physiol Heart Circ Physiol · April 1, 2017 Cardiac failure has been widely associated with an increase in glucose utilization. The aim of our study was to identify factors that mechanistically bridge this link between hyperglycemia and heart failure. Here, we screened the Hybrid Mouse Diversity Pan ... Full text Link to item Cite

A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.

Journal Article JACC Basic Transl Sci · March 2017 Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evide ... Full text Link to item Cite

Light-sheet fluorescence imaging to localize cardiac lineage and protein distribution.

Journal Article Sci Rep · February 6, 2017 Light-sheet fluorescence microscopy (LSFM) serves to advance developmental research and regenerative medicine. Coupled with the paralleled advances in fluorescence-friendly tissue clearing technique, our cardiac LSFM enables dual-sided illumination to rapi ... Full text Link to item Cite

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

Journal Article Cell Stem Cell · February 2, 2017 Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances ... Full text Link to item Cite

Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.

Journal Article Cell Syst · January 25, 2017 We previously reported a genetic analysis of heart failure traits in a population of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to perform a sy ... Full text Link to item Cite

A Path to Implement Precision Child Health Cardiovascular Medicine.

Journal Article Front Cardiovasc Med · 2017 Congenital heart defects (CHDs) affect approximately 1% of live births and are a major source of childhood morbidity and mortality even in countries with advanced healthcare systems. Along with phenotypic heterogeneity, the underlying etiology of CHDs is m ... Full text Link to item Cite

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

Journal Article Front Physiol · 2017 Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (KrĂĽppel-like factor 15) is a transcription factor and maste ... Full text Link to item Cite

Inflammatory and apoptotic remodeling in autonomic nervous system following myocardial infarction.

Journal Article PLoS One · 2017 BACKGROUND: Chronic myocardial infarction (MI) triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS), including stellate ganglia (SG) and dorsal root ganglia (DRG) contribute to in ... Full text Link to item Cite

Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.

Journal Article J Mol Cell Cardiol · December 2016 Branched chain α-keto acids (BCKAs) are endogenous metabolites of branched-chain amino acids (BCAAs). BCAA and BCKA are significantly elevated in pathologically stressed heart and contribute to chronic pathological remodeling and dysfunction. However, thei ... Full text Link to item Cite

Branched chain amino acid metabolic reprogramming in heart failure.

Journal Article Biochim Biophys Acta · December 2016 Metabolic remodeling is a hall-mark of cardiac maturation and pathology. The switch of substrate utilization from glucose to fatty acid is observed during post-natal maturation period in developing heart, but the process is reversed from fatty acids to glu ... Full text Link to item Cite

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.

Journal Article Am J Physiol Heart Circ Physiol · November 1, 2016 All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in th ... Full text Link to item Cite

Operationalizing Precision Cardiovascular Medicine: Three Innovations.

Journal Article Circ Res · October 14, 2016 For precision medicine to become a reality, we propose three changes. First, healthcare deliverables must be prioritized, enabling translation of knowledge to the clinic. Second, physicians and patients must be convinced to participate, requiring additiona ... Full text Link to item Cite

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

Journal Article Circ Cardiovasc Genet · October 2016 BACKGROUND: Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programmi ... Full text Link to item Cite

The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy.

Journal Article Nat Med · October 2016 Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (lnc)RNA, named ca ... Full text Link to item Cite

Deconvolution of the Human Endothelial Transcriptome.

Journal Article Cell Syst · September 28, 2016 A systems approach deconvolutes genes specific to and enriched in endothelium from whole-organ transcriptome data, with applications to other cell types and tissues. ... Full text Link to item Cite

Relationship of disease-associated gene expression to cardiac phenotype is buffered by genetic diversity and chromatin regulation.

Journal Article Physiol Genomics · August 1, 2016 Expression of a cohort of disease-associated genes, some of which are active in fetal myocardium, is considered a hallmark of transcriptional change in cardiac hypertrophy models. How this transcriptome remodeling is affected by the common genetic variatio ... Full text Link to item Cite

Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins Hmgb and Ctcf: IMPLICATIONS FOR TRANSCRIPTIONAL REGULATION.

Journal Article J Biol Chem · July 22, 2016 Transcriptome remodeling in heart disease occurs through the coordinated actions of transcription factors, histone modifications, and other chromatin features at pathology-associated genes. The extent to which genome-wide chromatin reorganization also cont ... Full text Link to item Cite

Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

Journal Article PLoS Genet · July 2016 We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and func ... Full text Link to item Cite

The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits.

Journal Article J Lipid Res · June 2016 The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping gen ... Full text Link to item Cite

Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure.

Journal Article Circulation · May 24, 2016 BACKGROUND: Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudie ... Full text Link to item Cite

p38α MAPK Regulates Lineage Commitment and OPG Synthesis of Bone Marrow Stromal Cells to Prevent Bone Loss under Physiological and Pathological Conditions.

Journal Article Stem Cell Reports · April 12, 2016 Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes. Skewed differentiation of BM-MSCs contributes to the pathogenesis of osteoporosis. Yet how BM-MSC lineage commitment is r ... Full text Link to item Cite

DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States.

Journal Article Circ Res · March 4, 2016 RATIONALE: Only a small portion of the known heritability of cardiovascular diseases, such as heart failure, can be explained based on single-gene mutations. Chromatin structure and regulation provide a substrate through which genetic differences in noncod ... Full text Link to item Cite

Rescue of Pressure Overload-Induced Heart Failure by Estrogen Therapy.

Journal Article J Am Heart Assoc · January 22, 2016 BACKGROUND: Estrogen pretreatment has been shown to attenuate the development of heart hypertrophy, but it is not known whether estrogen could also rescue heart failure (HF). Furthermore, the heart has all the machinery to locally biosynthesize estrogen vi ... Full text Link to item Cite

p38 MAP kinases in the heart.

Journal Article Gene · January 10, 2016 p38 kinases are members of the mitogen-activated protein kinases (MAPK) with established contribution to a wide range of signaling pathways and different biological processes. The prototypic p38 MAPK, p38α was originally identified as an essential signalin ... Full text Link to item Cite

RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.

Journal Article J Clin Invest · January 2016 RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and ... Full text Link to item Cite

Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells.

Journal Article Acta Pharmacol Sin · December 2015 AIM: The mitochondrial targeted 2C-type serine/threonine protein phosphatase (PP2Cm) is encoded by the gene PPM1K and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. It ... Full text Link to item Cite

M1 of Murine Gamma-Herpesvirus 68 Induces Endoplasmic Reticulum Chaperone Production.

Journal Article Sci Rep · November 30, 2015 Viruses rely on host chaperone network to support their infection. In particular, the endoplasmic reticulum (ER) resident chaperones play key roles in synthesizing and processing viral proteins. Influx of a large amount of foreign proteins exhausts the fol ... Full text Link to item Cite

The elusive philosopher's stone in young blood.

Journal Article Circ Res · November 6, 2015 Full text Link to item Cite

Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and impaired cardiac adaptation.

Journal Article J Biol Chem · October 30, 2015 Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (mus ... Full text Link to item Cite

A H(a)rd Way to Adapt in Cardiac Hypertrophy.

Journal Article Circ Res · August 28, 2015 Full text Link to item Cite

High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping.

Journal Article G3 (Bethesda) · July 28, 2015 Human genome-wide association studies have identified thousands of loci associated with disease phenotypes. Genome-wide association studies also have become feasible using rodent models and these have some important advantages over human studies, including ... Full text Link to item Cite

Genetics of common forms of heart failure: challenges and potential solutions.

Journal Article Curr Opin Cardiol · May 2015 PURPOSE OF REVIEW: In contrast to many other human diseases, the use of genome-wide association studies (GWAS) to identify genes for heart failure (HF) has had limited success. We will discuss the underlying challenges as well as potential new approaches t ... Full text Link to item Cite

Mapping genetic contributions to cardiac pathology induced by Beta-adrenergic stimulation in mice.

Journal Article Circ Cardiovasc Genet · February 2015 BACKGROUND: Chronic stress-induced cardiac pathology exhibits both a wide range in severity and a high degree of heterogeneity in clinical manifestation in human patients. This variability is contributed to by complex genetic and environmental etiologies w ... Full text Link to item Cite

Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy.

Journal Article J Mol Cell Cardiol · February 2015 Defect in mitochondrial biogenesis and cardiac energy metabolism is a critical contributing factor to cardiac hypertrophy and heart failure. Sentrin/SUMO specific protease 1 (SENP1) mediated regulation of PGC-1α transcriptional activity plays an essential ... Full text Link to item Cite

Dawn of the Epi-LncRNAs: new path from Myheart.

Journal Article Circ Res · January 16, 2015 Myheart is a cardiac specific long-noncoding (lnc) RNA with targeted modulation of chromatin modifying SWI/SNF complex via direct interaction with Brg1. Genetic induction of Myheart in mouse heart has a significant protective effect against the pathogenesi ... Full text Link to item Cite

Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway

Journal Article FEBS Open Bio · January 1, 2015 Activation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The pr ... Full text Cite

Branched Chain Amino Acids in Heart Failure

Chapter · January 1, 2015 Branched-Chain Amino Acids (BCAA) are essential amino acids for protein synthesis and also serve as critical signaling molecules for cellular growth and metabolic regulations. The homeostasis of BCAA is regulated by food uptake and intrinsic catabolic acti ... Full text Cite

Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells.

Journal Article Dev Cell · December 22, 2014 Acquisition and maintenance of vascular smooth muscle fate are essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMCs) can result in structura ... Full text Link to item Cite

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.

Journal Article J Clin Invest · April 2014 Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and de ... Full text Link to item Cite

IRE1 phosphatase PP2Ce regulates adaptive ER stress response in the postpartum mammary gland.

Journal Article PLoS One · 2014 We recently reported that the PPM1l gene encodes an endoplasmic reticulum (ER) membrane targeted protein phosphatase (named PP2Ce) with highly specific activity towards Inositol-requiring protein-1 (IRE1) and regulates the functional outcome of ER stress. ... Full text Link to item Cite

Transcriptome complexity in cardiac development and diseases--an expanding universe between genome and phenome.

Journal Article Circ J · 2014 With the advancement of transcriptome profiling by micro-arrays and high-throughput RNA-sequencing, transcriptome complexity and its dynamics are revealed at different levels in cardiovascular development and diseases. In this review, we will highlight the ... Full text Link to item Cite

Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes.

Journal Article Am J Physiol Heart Circ Physiol · December 1, 2013 Myocyte hypertrophy antecedent to heart failure involves changes in global gene expression, although the preceding mechanisms to coordinate DNA accessibility on a genomic scale are unknown. Chromatin-associated proteins alter chromatin structure by changin ... Full text Link to item Cite

Nuclear phosphatase PPM1G in cellular survival and neural development.

Journal Article Dev Dyn · September 2013 BACKGROUND: PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown. RESULTS: Here we show that ppm1g expression is highly enric ... Full text Link to item Cite

Divergent mitochondrial biogenesis responses in human cardiomyopathy.

Journal Article Circulation · May 14, 2013 BACKGROUND: Mitochondria are key players in the development and progression of heart failure (HF). Mitochondrial (mt) dysfunction leads to diminished energy production and increased cell death contributing to the progression of left ventricular failure. Th ... Full text Link to item Cite

PPM1l encodes an inositol requiring-protein 1 (IRE1) specific phosphatase that regulates the functional outcome of the ER stress response.

Journal Article Mol Metab · 2013 The protein phosphatase 1-like gene (PPM1l) was identified as causal gene for obesity and metabolic abnormalities in mice. However, the underlying mechanisms were unknown. In this report, we find PPM1l encodes an endoplasmic reticulum (ER) membrane targete ... Full text Link to item Cite

Creatine kinase-overexpression improves myocardial energetics, contractile dysfunction and survival in murine doxorubicin cardiotoxicity.

Journal Article PLoS One · 2013 Doxorubicin (DOX) is a commonly used life-saving antineoplastic agent that also causes dose-dependent cardiotoxicity. Because ATP is absolutely required to sustain normal cardiac contractile function and because impaired ATP synthesis through creatine kina ... Full text Link to item Cite

Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome.

Journal Article Development · December 1, 2012 The Notch signaling pathway is an important contributor to the development and homeostasis of the cardiovascular system. Not surprisingly, mutations in Notch receptors and ligands have been linked to a variety of hereditary diseases that impact both the he ... Full text Link to item Cite

BCVS scientific conference 2012 meeting report.

Journal Article Circ Res · October 12, 2012 Full text Link to item Cite

Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits.

Journal Article Mamm Genome · October 2012 We have developed an association-based approach using classical inbred strains of mice in which we correct for population structure, which is very extensive in mice, using an efficient mixed-model algorithm. Our approach includes inbred parental strains as ... Full text Link to item Cite

Creatine kinase overexpression improves ATP kinetics and contractile function in postischemic myocardium.

Journal Article Am J Physiol Heart Circ Physiol · October 1, 2012 Reduced myofibrillar ATP availability during prolonged myocardial ischemia may limit post-ischemic mechanical function. Because creatine kinase (CK) is the prime energy reserve reaction of the heart and because it has been difficult to augment ATP synthesi ... Full text Link to item Cite

"Good enough solutions" and the genetics of complex diseases.

Journal Article Circ Res · August 3, 2012 In this Emerging Science Review, we discuss a systems genetics strategy, which we call gene module association study (GMAS), as a novel approach complementing genome-wide association studies (GWAS), to understand complex diseases by focusing on how genes w ... Full text Link to item Cite

Global impact of RNA splicing on transcriptome remodeling in the heart.

Journal Article J Zhejiang Univ Sci B · August 2012 In the eukaryotic transcriptome, both the numbers of genes and different RNA species produced by each gene contribute to the overall complexity. These RNA species are generated by the utilization of different transcriptional initiation or termination sites ... Full text Link to item Cite

Tissue-specific and nutrient regulation of the branched-chain α-keto acid dehydrogenase phosphatase, protein phosphatase 2Cm (PP2Cm).

Journal Article J Biol Chem · July 6, 2012 Branched-chain amino acid (BCAA) homeostasis is maintained through highly regulated catabolic activities where the rate-limiting step is catalyzed by branched-chain α-keto dehydrogenase (BCKD). Our previous study has identified a mitochondria-targeted prot ... Full text Link to item Cite

Cardiac vulnerability to ischemia/reperfusion injury drastically increases in late pregnancy.

Journal Article Basic Res Cardiol · July 2012 Although the murine late pregnant (LP) heart is speculated to be a better functioning heart during physiological conditions, the susceptibility of LP hearts to I/R injury is still unknown. The aims of this study were to investigate the cardiac vulnerabilit ... Full text Link to item Cite

Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth.

Journal Article Mol Cell Proteomics · June 2012 A fundamental question in biology is how genome-wide changes in gene expression are enacted in response to a finite stimulus. Recent studies have mapped changes in nucleosome localization, determined the binding preferences for individual transcription fac ... Full text Link to item Cite

Klf15 orchestrates circadian nitrogen homeostasis.

Journal Article Cell Metab · March 7, 2012 Diurnal variation in nitrogen homeostasis is observed across phylogeny. But whether these are endogenous rhythms, and if so, molecular mechanisms that link nitrogen homeostasis to the circadian clock remain unknown. Here, we provide evidence that a clock-d ... Full text Link to item Cite

Cdc37/Hsp90 protein-mediated regulation of IRE1α protein activity in endoplasmic reticulum stress response and insulin synthesis in INS-1 cells.

Journal Article J Biol Chem · February 24, 2012 IRE1α is an endoplasmic reticulum (ER) localized signaling molecule critical for unfolded protein response. During ER stress, IRE1α activation is induced by oligomerization and autophosphorylation in its cytosolic domain, a process triggered by dissociatio ... Full text Link to item Cite

Novel Ser/Thr protein phosphatases in cell death regulation.

Journal Article Physiology (Bethesda) · February 2012 Cell death is regulated by a myriad of intracellular molecular pathways, with many involving protein phosphorylation and dephosphorylation. In this review, we will focus on Ser/Thr phosphatases-mediated regulation in cell apoptosis as well as on their pote ... Full text Link to item Cite

p38Îł activity is required for maintenance of slow skeletal muscle size.

Journal Article Muscle Nerve · February 2012 INTRODUCTION: p38Îł kinase is highly enriched in skeletal muscle and is implicated in myotube formation. However, the activation status of p38Îł in muscle is unclear. METHODS: p38Îł activity in slow and fast adult mouse skeletal muscle tissue was examined, as ... Full text Link to item Cite

Gi-biased β2AR signaling links GRK2 upregulation to heart failure.

Journal Article Circ Res · January 20, 2012 RATIONALE: Phosphorylation of β(2)-adrenergic receptor (β(2)AR) by a family of serine/threonine kinases known as G protein-coupled receptor kinase (GRK) and protein kinase A (PKA) is a critical determinant of cardiac function. Upregulation of G protein-cou ... Full text Open Access Link to item Cite

Systems-based approaches to cardiovascular disease.

Journal Article Nat Rev Cardiol · January 10, 2012 Common cardiovascular diseases, such as atherosclerosis and congestive heart failure, are exceptionally complex, involving a multitude of environmental and genetic factors that often show nonlinear interactions as well as being highly dependent on sex, age ... Full text Link to item Cite

Creatine kinase-mediated improvement of function in failing mouse hearts provides causal evidence the failing heart is energy starved.

Journal Article J Clin Invest · January 2012 ATP is required for normal cardiac contractile function, and it has long been hypothesized that reduced energy delivery contributes to the contractile dysfunction of heart failure (HF). Despite experimental and clinical HF data showing reduced metabolism t ... Full text Link to item Cite

Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts.

Journal Article Circ Res · December 9, 2011 RATIONALE: Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac ... Full text Link to item Cite

Protective role of transient pore openings in calcium handling by cardiac mitochondria.

Journal Article J Biol Chem · October 7, 2011 Long-lasting mitochondrial permeability transition pore (mPTP) openings damage mitochondria, but transient mPTP openings protect against chronic cardiac stress. To probe the mechanism, we subjected isolated cardiac mitochondria to gradual Ca(2+) loading, w ... Full text Link to item Cite

The p38 mitogen-activated protein kinase pathway--a potential target for intervention in infarction, hypertrophy, and heart failure.

Journal Article J Mol Cell Cardiol · October 2011 The p38 mitogen-activated protein kinases (p38s) are stress-activated Ser/Thr kinases. Their activation has been associated with various pathological stressors in the heart. Activated p38 is implicated in a wide spectrum of cardiac pathologies, including h ... Full text Link to item Cite

Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit?

Journal Article Cardiovasc Res · May 1, 2011 Metabolic remodelling is an integral part of the pathogenesis of heart failure. Although much progress has been made in our current understanding of the metabolic impairment involving carbohydrates and fatty acids in failing hearts, relatively little is kn ... Full text Link to item Cite

Catabolism of branched-chain amino acids in heart failure: insights from genetic models.

Conference Pediatr Cardiol · March 2011 Genetic defects in amino acid metabolism are major causes of newborn diseases that often lead to abnormal development and function of the central nervous system. Their direct impact on cardiac development and function has rarely been investigated. Recently ... Full text Link to item Cite

Restriction of big hearts by a small RNA.

Journal Article Circ Res · February 4, 2011 Full text Link to item Cite

Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin.

Journal Article Hum Mol Genet · February 1, 2011 Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutant prelamin A, progerin, that terminates with a farnesylcysteine. HGPS knock-in mice (Lmna(HG/+)) develop severe progeria-like disease phenotypes. These phenotypes can be ameliorated with a pro ... Full text Link to item Cite

Phosphoproteome analysis reveals regulatory sites in major pathways of cardiac mitochondria.

Journal Article Mol Cell Proteomics · February 2011 Mitochondrial functions are dynamically regulated in the heart. In particular, protein phosphorylation has been shown to be a key mechanism modulating mitochondrial function in diverse cardiovascular phenotypes. However, site-specific phosphorylation infor ... Full text Link to item Cite

Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5.

Journal Article J Am Coll Cardiol · December 7, 2010 OBJECTIVES: we tested the hypothesis that bi-directional, gene-targeted regulation of cardiomyocyte cyclic guanosine monophosphate-selective phosphodiesterase type 5 (PDE5) influences maladaptive remodeling in hearts subjected to sustained pressure overloa ... Full text Link to item Cite

Electrochemical properties and myocyte interaction of carbon nanotube microelectrodes.

Journal Article Nano Lett · November 10, 2010 Arrays of carbon nanotube (CNT) microelectrodes (nominal geometric surface areas 20-200 ÎĽm(2)) were fabricated by photolithography with chemical vapor deposition of randomly oriented CNTs. Raman spectroscopy showed strong peak intensities in both G and D b ... Full text Link to item Cite

Differential regulation of proteasome function in isoproterenol-induced cardiac hypertrophy.

Journal Article Circ Res · October 29, 2010 RATIONALE: Proteasomal degradation is altered in many disease phenotypes including cardiac hypertrophy, a prevalent condition leading to heart failure. Our recent investigations identified heterogeneous subpopulations of proteasome complexes in the heart a ... Full text Link to item Cite

Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale.

Journal Article Physiol Rev · October 2010 Among the myriad of intracellular signaling networks that govern the cardiac development and pathogenesis, mitogen-activated protein kinases (MAPKs) are prominent players that have been the focus of extensive investigations in the past decades. The four be ... Full text Link to item Cite

Targeted disruption of Mapk14 (p38MAPKalpha) in granulosa cells and cumulus cells causes cell-specific changes in gene expression profiles that rescue COC expansion and maintain fertility.

Journal Article Mol Endocrinol · September 2010 MAPK14 (p38MAPKalpha) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. ... Full text Link to item Cite

Preserved heart function and maintained response to cardiac stresses in a genetic model of cardiomyocyte-targeted deficiency of cyclooxygenase-2.

Journal Article J Mol Cell Cardiol · August 2010 Cyclooxygenase-1 and -2 are rate-limiting enzymes in the formation of a wide array of bioactive lipid mediators collectively known as prostanoids (prostaglandins, prostacyclins, and thromboxanes). Evidence from clinical trials shows that selective inhibiti ... Full text Link to item Cite

An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria.

Journal Article Hum Mol Genet · July 1, 2010 Lamin A is formed from prelamin A by four post-translational processing steps-farnesylation, release of the last three amino acids of the protein, methylation of the farnesylcysteine and the endoproteolytic release of the C-terminal 15 amino acids (includi ... Full text Link to item Cite

Compensatory hypertrophy induced by ventricular cardiomyocyte-specific COX-2 expression in mice.

Journal Article J Mol Cell Cardiol · July 2010 Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases owing to the finding that highly specific COX-2 inhibitors (i.e., Vioxx) i ... Full text Link to item Cite

Post-translational regulation of calsarcin-1 during pressure overload-induced cardiac hypertrophy.

Journal Article J Mol Cell Cardiol · June 2010 Chronic pressure overload to the heart leads to cardiac hypertrophy and failure through processes that involve reorganization of subcellular compartments and alteration of established signaling mechanisms. To identify proteins contributing to this process, ... Full text Link to item Cite

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.

Journal Article J Clin Invest · May 2010 In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPARgamma coactivator-1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, ... Full text Link to item Cite

MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart.

Journal Article Circ Res · April 30, 2010 RATIONALE: Activation of p38 mitogen-activated protein kinase (MAPK) has a significant impact on cardiac gene expression, contractility, extracellular matrix remodeling, and inflammatory response in heart. The p38 kinase pathway also has a controversial ro ... Full text Link to item Cite

Specific regulation of noncanonical p38alpha activation by Hsp90-Cdc37 chaperone complex in cardiomyocyte.

Journal Article Circ Res · April 30, 2010 RATIONALE: p38 is an important stress activated protein kinase involved in gene regulation, proliferation, differentiation, and cell death regulation in heart. p38 kinase activity can be induced through canonical pathway via upstream kinases or by noncanon ... Full text Link to item Cite

Mice carrying a conditional Serca2(flox) allele for the generation of Ca(2+) handling-deficient mouse models.

Journal Article Cell Calcium · September 2009 Sarco(endo)plasmic reticulum calcium ATPases (SERCA) are cellular pumps that transport Ca(2+) into the sarcoplasmic reticulum (SR). Serca2 is the most widely expressed gene family member. The very early embryonic lethality of Serca2(null) mouse embryos has ... Full text Link to item Cite

Effect of p38 MAP kinases on contractility and ischemic injury in intact heart.

Journal Article Acta Physiol Hung · September 2009 The p38 MAP kinases are stress-activated MAP kinases whose induction is often associated with the onset of heart failure. This study investigated the role of p38 MAP kinase isoforms in the regulation of myocardial contractility and ischemia/reperfusion inj ... Full text Link to item Cite

Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene.

Journal Article J Mol Cell Cardiol · August 2009 The sarco(endo)plasmic reticulum calcium ATPase 2 (SERCA2) transports Ca(2+) from cytosol into the sarcoplasmic reticulum (SR) of cardiomyocytes, thereby maintaining the store of releasable Ca(2+) necessary for contraction. Reduced SERCA function has been ... Full text Link to item Cite

Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells.

Journal Article J Clin Invest · June 2009 The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain- ... Full text Link to item Cite

Macrophage deficiency of p38alpha MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice.

Journal Article J Clin Invest · April 2009 ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stress-induced apoptosis may affect advanced atherosclerosis. ... Full text Link to item Cite

Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K.

Journal Article Circ Res · February 27, 2009 The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-Apoe(-/-) mice bearing a null mutation in the Npc1 gene display prominent medial eros ... Full text Link to item Cite

Inducible and cardiac specific PTEN inactivation protects ischemia/reperfusion injury.

Journal Article J Mol Cell Cardiol · February 2009 PTEN is a dual lipid and protein phosphatase that antagonizes PI3K as well as other signaling pathways and regulates cellular survival and growth. However, its potential role in cardiac ischemia/reperfusion injury remains unknown. We established a transgen ... Full text Link to item Cite

Functional characterization of a mitochondrial Ser/Thr protein phosphatase in cell death regulation.

Book · 2009 Protein phosphorylation is a major form of posttranslational modification critical to cell signaling that also occurs in mitochondrial proteome. Yet, only very limited studies have been performed to characterize mitochondrial-targeted protein kinases or ph ... Full text Link to item Cite

Loss of Bmx nonreceptor tyrosine kinase prevents pressure overload-induced cardiac hypertrophy.

Journal Article Circ Res · December 5, 2008 Bmx nonreceptor tyrosine kinase has an established role in endothelial and lymphocyte signaling; however, its role in the heart is unknown. To determine whether Bmx participates in cardiac growth, we subjected mice deficient in the molecule (Bmx knockout m ... Full text Link to item Cite

A new (heat) shocking player in cardiac hypertrophy.

Journal Article Circ Res · November 21, 2008 Hypertrophic growth of cardiac myocytes is a common result of different physiological and pathological stresses. It remains a subject of considerable debate whether hypertrophy is a compensatory process that becomes maladaptive in diseased hearts or a dire ... Full text Link to item Cite

Proteomic insights into cardiac cell death and survival.

Journal Article Proteomics Clin Appl · June 2008 Cardiovascular disease is the leading cause of death and disability in the developed world. To design novel therapeutic strategies to treat and prevent this disease, better understanding of cardiac cell function is necessary. In addition to (and, indeed, i ... Full text Link to item Cite

Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family.

Journal Article Clin Exp Pharmacol Physiol · February 2008 1. The Type 2C protein phosphatases (PP2C) represent a highly conserved gene family in the mammalian genome. Recent studies have revealed that PP2C isoforms possess unique patterns of tissue and subcellular distribution associated with diverse functionalit ... Full text Link to item Cite

The role of COX-2 in heart pathology.

Journal Article Cardiovasc Hematol Agents Med Chem · January 2008 Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins, and an important anti-inflammation drug target. Recent focus has been placed on the role of COX-2 in heart function and pathology, due to the finding that specific COX-2 inhibito ... Full text Link to item Cite

Mitogen-activated protein kinases in heart development and diseases.

Journal Article Circulation · September 18, 2007 Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, ha ... Full text Link to item Cite

Gi alpha 1-mediated cardiac electrophysiological remodeling and arrhythmia in hypertrophic cardiomyopathy.

Journal Article Circulation · August 7, 2007 BACKGROUND: Cardiac hypertrophy is a major risk factor for arrhythmias and sudden cardiac death. However, the underlying signaling mechanisms involved in the induction of arrhythmia and electrophysiological remodeling in cardiac hypertrophy are unclear. ME ... Full text Link to item Cite

Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2-adrenergic receptor, but not beta 1-adrenergic receptor.

Journal Article J Clin Invest · May 2007 We examined the role of p38alpha MAPK in mediating cardiomyopathy in mice overexpressing beta(1)-adrenergic receptor (beta(1)-AR) or beta(2)-AR by mating them with dominant-negative p38alpha (DNp38alpha) MAPK mice. Both beta(1)-AR and beta(2)-AR Tg mice ha ... Full text Link to item Cite

A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development.

Journal Article Genes Dev · April 1, 2007 Mitochondria play a central role in the regulation of programmed cell death signaling. Here, we report the finding of a mitochondrial matrix-targeted protein phosphatase 2C family member (PP2Cm) that regulates mitochondrial membrane permeability transition ... Full text Link to item Cite

Role of an alternatively spliced form of alphaII-spectrin in localization of connexin 43 in cardiomyocytes and regulation by stress-activated protein kinase.

Journal Article J Mol Cell Cardiol · March 2007 Decreases in the expression of connexin 43 and the integrity of gap junctions in cardiac muscle, induced by the constitutive activation of the c-Jun N-terminal kinase (JNK) signaling pathway, have been linked to conduction defects and sudden cardiac failur ... Full text Link to item Cite

p38-MAPK induced dephosphorylation of alpha-tropomyosin is associated with depression of myocardial sarcomeric tension and ATPase activity.

Journal Article Circ Res · February 16, 2007 Our objective in work presented here was to understand the mechanisms by which activated p38alpha MAPK depresses myocardial contractility. To test the hypothesis that activation of p38 MAPK directly influences sarcomeric function, we used transgenic mouse ... Full text Link to item Cite

Heart hypertrophy during pregnancy: a better functioning heart?

Journal Article Trends Cardiovasc Med · November 2006 During pregnancy, healthy women develop ventricular hypertrophy and diastolic dysfunction as a result of volume overload as well as increased stretch and force demand. Pregnancy also induces electrocardiogram disturbances such as longer QT-interval dispers ... Full text Link to item Cite

Pressure overload induces greater hypertrophy and mortality in female mice with p38alpha MAPK inhibition.

Journal Article J Mol Cell Cardiol · October 2006 We examined pressure overload left ventricular (LV) hypertrophy (H) induced by aortic banding in transgenic mice with cardiac-specific expression of a dominant negative (DN) p38alpha (TG) and wild type controls (WT). In response to chronic pressure overloa ... Full text Link to item Cite

Overexpression of bone morphogenetic protein 10 in myocardium disrupts cardiac postnatal hypertrophic growth.

Journal Article J Biol Chem · September 15, 2006 Postnatal cardiac hypertrophies have traditionally been classified into physiological or pathological hypertrophies. Both of them are induced by hemodynamic load. Cardiac postnatal hypertrophic growth is regarded as a part of the cardiac maturation process ... Full text Link to item Cite

JNK activation decreases PP2A regulatory subunit B56alpha expression and mRNA stability and increases AUF1 expression in cardiomyocytes.

Journal Article Am J Physiol Heart Circ Physiol · September 2006 A central feature of heart disease is a molecular remodeling of signaling pathways in cardiac myocytes. This study focused on novel molecular elements of MAPK-mediated alterations in the pattern of gene expression of the protein phosphatase 2A (PP2A). In a ... Full text Link to item Cite

Myocardin induces cardiomyocyte hypertrophy.

Journal Article Circ Res · April 28, 2006 In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly of sarcomeres, and cellular enlargement. We show that hypertrophic signals stimulate the expression and transcri ... Full text Link to item Cite

Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation.

Journal Article Physiol Genomics · March 13, 2006 Three major MAP kinase signaling cascades, ERK, p38, and JNK, play significant roles in the development of cardiac hypertrophy and heart failure in response to external stress and neural/hormonal stimuli. To study the specific function of each MAP kinase b ... Full text Link to item Cite

TAB-1 modulates intracellular localization of p38 MAP kinase and downstream signaling.

Journal Article J Biol Chem · March 3, 2006 Stress-activated mitogen-activated protein (MAP) kinase p38 mediates stress signaling in mammalian cells via threonine and tyrosine phosphorylation in its conserved TGY motif by upstream MAP kinase kinases (MKKs). In addition, p38 MAP kinase can also be ac ... Full text Link to item Cite

Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor.

Journal Article J Cell Biol · October 10, 2005 Macrophage death in advanced atherosclerosis promotes necrosis and plaque destabilization. A likely cause of macrophage death is accumulation of free cholesterol (FC) in the ER, leading to activation of the unfolded protein response (UPR) and C/EBP homolog ... Full text Link to item Cite

Molecular and functional signature of heart hypertrophy during pregnancy.

Journal Article Circ Res · June 10, 2005 During pregnancy, the heart develops a reversible physiological hypertrophic growth in response to mechanical stress and increased cardiac output; however, underlying molecular mechanisms remain unknown. Here, we investigated pregnancy-related changes in h ... Full text Link to item Cite

p38 MAP kinase mediates inflammatory cytokine induction in cardiomyocytes and extracellular matrix remodeling in heart.

Journal Article Circulation · May 17, 2005 BACKGROUND: Increasing evidence suggests that development of heart failure involves activation of stress-response inflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6. Yet, the myocyte contribution to their induction in failing h ... Full text Link to item Cite

p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.

Journal Article Genes Dev · May 15, 2005 Adult mammalian cardiomyocytes are considered terminally differentiated and incapable of proliferation. Consequently, acutely injured mammalian hearts do not regenerate, they scar. Here, we show that adult mammalian cardiomyocytes can divide. One important ... Full text Link to item Cite

Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load.

Journal Article J Clin Invest · May 2005 Cardiac pressure load stimulates hypertrophy, often leading to chamber dilation and dysfunction. ROS contribute to this process. Here we show that uncoupling of nitric oxide synthase-3 (NOS3) plays a major role in pressure load-induced myocardial ROS and c ... Full text Link to item Cite

Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction.

Journal Article J Mol Cell Cardiol · April 2005 Acute coronary occlusion results in ischemia-mediated death of cardiomyocytes. In the days and weeks following myocardial infarction (MI), left ventricular remodeling occurs that is characterized by persistent cardiomyocyte apoptosis, thinning and fibrosis ... Full text Link to item Cite

Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition.

Journal Article Am J Physiol Heart Circ Physiol · March 2005 Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a powerful late phase of cardioprotection against ischemia-reperfusion injury; however, t ... Full text Link to item Cite

Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy.

Journal Article Nat Med · February 2005 Sustained cardiac pressure overload induces hypertrophy and pathological remodeling, frequently leading to heart failure. Genetically engineered hyperstimulation of guanosine 3',5'-cyclic monophosphate (cGMP) synthesis counters this response. Here, we show ... Full text Link to item Cite

Junctophilin type 2 is associated with caveolin-3 and is down-regulated in the hypertrophic and dilated cardiomyopathies.

Journal Article Biochem Biophys Res Commun · December 17, 2004 Functional coupling between the sarcolemmal membrane and the sarcoplasmic reticulum is based on distinct structures called junctional membrane complexes (JMCs). Recently, junctophilins are found to be responsible for normal formation of JMCs. In the presen ... Full text Link to item Cite

Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defects.

Journal Article J Biol Chem · April 9, 2004 The stress-activated protein kinase, c-Jun N-terminal kinase (JNK), has been implicated in the process of cardiac hypertrophy and apoptosis, yet the specific roles of JNK in heart failure are unclear. To determine the effects of JNK activation in intact he ... Full text Link to item Cite

Modulation of in vivo cardiac function by myocyte-specific nitric oxide synthase-3.

Journal Article Circ Res · March 19, 2004 Nitric oxide (NO) functions principally as a diffusible paracrine effector. The exception is in cardiomyocytes where both NO synthases (NOS) and target proteins coexist, allowing NO to work in an autocrine/intracrine fashion. However, the most abundant myo ... Full text Link to item Cite

Lack of p38 MAP kinase activation in TRAIL-resistant cells is not related to the resistance to TRAIL-mediated cell death.

Journal Article Cancer Biol Ther · March 2004 Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediate ... Full text Link to item Cite

Stress-activated MAP kinases in cardiac remodeling and heart failure; new insights from transgenic studies.

Journal Article Trends Cardiovasc Med · February 2004 Activation of stress-activated mitogen-activated protein kinases (SAPKs), mainly c-Jun N-terminal kinase (JNK) and p38, have long been associated with different forms of cardiac pathology across a wide spectrum of species. However, their specific roles in ... Full text Link to item Cite

Sarcoplasmic reticulum calcium defect in Ras-induced hypertrophic cardiomyopathy heart.

Journal Article Am J Physiol Heart Circ Physiol · January 2004 The small G protein Ras-mediated signaling pathway has been implicated in the development of hypertrophy and diastolic dysfunction in the heart. Earlier cellular studies have suggested that the Ras pathway is responsible for reduced L-type calcium channel ... Full text Link to item Cite

Neuro-hormonal integration of metabolism: challenges and opportunities in the postgenomic era.

Journal Article NestlĂ© Nutrition workshop series. Clinical & performance programme · January 1, 2004 Cite

Robust adenoviral and adeno-associated viral gene transfer to the in vivo murine heart: application to study of phospholamban physiology.

Journal Article Circulation · December 2, 2003 BACKGROUND: Viral gene transfer to the whole heart in vivo has been achieved in several mammalian species but remained difficult to accomplish in murine hearts. We postulated that a key impediment derives from the use of proximal aortic occlusion during vi ... Full text Link to item Cite

Role of 14-3-3-mediated p38 mitogen-activated protein kinase inhibition in cardiac myocyte survival.

Journal Article Circ Res · November 28, 2003 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates As ... Full text Link to item Cite

Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells.

Journal Article J Biol Chem · May 23, 2003 The efficacy of cisplatin in cancer chemotherapy is limited by the development of resistance. Although the molecular mechanisms involved in chemoresistance are poorly understood, cellular response to cisplatin is known to involve activation of MAPK and oth ... Full text Link to item Cite

Calmodulin regulation of excitation-contraction coupling in cardiac myocytes.

Journal Article Circ Res · April 4, 2003 Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key molecules involved in excitation-contraction (EC) coupling. In the present study, we report that adenoviral expression of a mutant CaM lacking all of its four Ca2+-binding sites, CaM( ... Full text Link to item Cite

Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination.

Journal Article FASEB J · April 2003 Using a cre-loxP-mediated gene-switch approach, we achieved targeted JNK activation in adult hearts. A transgenic model is established carrying a floxed gene-switch construct that directs GFP marker gene expression in the absence of DNA recombination betwe ... Full text Link to item Cite

Atrial chamber-specific expression of sarcolipin is regulated during development and hypertrophic remodeling.

Journal Article J Biol Chem · March 14, 2003 Intracellular Ca2+ regulation is critical in the normal cardiac function and development of pathologic hearts. Phospholamban, an endogenous inhibitor of sarcoplasmic reticulum Ca2+ ATPase in the sarcoplasmic reticulum, plays an important role in Ca2+ cycli ... Full text Link to item Cite

The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis.

Journal Article J Clin Invest · March 2003 Cardiac hypertrophy is a common response to pressure overload and is associated with increased mortality. Mechanical stress in the heart can result in the integrin-mediated activation of focal adhesion kinase and the subsequent recruitment of the Grb2 adap ... Full text Link to item Cite

Novel regulation of cardiac force-frequency relation by CREM (cAMP response element modulator).

Journal Article FASEB J · February 2003 The cAMP response element modulator (CREM) plays pivotal roles in the hypothalamic-pituitary-gonadal axis. CREM mRNA is robustly expressed in human myocardium, and identified isoforms may suppress cAMP response element-mediated transcription. However, litt ... Full text Link to item Cite

Recombinant adenoviral expression of dominant negative IkappaBalpha protects brain from cerebral ischemic injury.

Journal Article Biochem Biophys Res Commun · November 22, 2002 Transcription factor NF-kappaB is associated with inflammatory response and cell survival. Under inactive condition, NF-kappaB is sequestered in the cytoplasm by an anchor protein, inhibitor of NF-kappaB (IkappaB). NF-kappaB was shown to be activated durin ... Full text Link to item Cite

c-Jun N-terminal kinase activation mediates downregulation of connexin43 in cardiomyocytes.

Journal Article Circ Res · October 4, 2002 Loss of gap junctions and impaired intercellular communication are characteristic features of pathological remodeling in heart failure as a result of stress or injury, yet the underlying regulatory mechanism has not been identified. Here, we report that in ... Full text Link to item Cite

Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.

Journal Article Nat Med · August 2002 The feasibility of gene therapy for cardiomyopathy, heart failure and other chronic cardiac muscle diseases is so far unproven. Here, we developed an in vivo recombinant adeno-associated virus (rAAV) transcoronary delivery system that allows stable, high e ... Full text Link to item Cite

Induction of apoptosis in vascular smooth muscle cells by mechanical stretch.

Journal Article Am J Physiol Heart Circ Physiol · May 2002 We studied the response of porcine vascular smooth muscle cells (PVSMCs) to cyclic sinusoidal stretch at a frequency of 1 Hz. Cyclic stretch with an area change of 25% caused an increase in PVSMC apoptosis, which was accompanied by sustained activation of ... Full text Link to item Cite

An increase in the myocardial PCr/ATP ratio in GLUT4 null mice.

Journal Article FASEB J · April 2002 ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several patho ... Full text Link to item Cite

p38 Mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes.

Journal Article Circ Res · February 8, 2002 p38 Mitogen-activated protein kinase (MAPK) is one of the most ancient signaling molecules and is involved in multiple cellular processes, including cell proliferation, cell growth, and cell death. In the heart, enhanced activation of p38 MAPK is associate ... Full text Link to item Cite

Using a gene-switch transgenic approach to dissect distinct roles of MAP kinases in heart failure.

Conference Cold Spring Harb Symp Quant Biol · 2002 We have demonstrated that Cre-loxP-mediated gene-switch transgenesis is an effective approach to achieve targeted and temporally regulated gene manipulation in the heart. Using this approach, we have established animal models with targeted activation of di ... Full text Link to item Cite

In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein.

Journal Article Circulation · October 23, 2001 BACKGROUND: A variety of pathologic stimuli lead to apoptosis of cardiomyocytes. Survival factors like insulin-like growth factor-I (IGF-I) exert anti-apoptotic effects in the heart. Yet the underlying signaling pathways are poorly understood. METHODS AND ... Full text Link to item Cite

The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy.

Journal Article Proc Natl Acad Sci U S A · October 9, 2001 Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP kinase in ventricular myocytes was achieved in vivo by us ... Full text Link to item Cite

Signal transduction in cardiac hypertrophy--dissecting compensatory versus pathological pathways utilizing a transgenic approach.

Journal Article Curr Opin Pharmacol · April 2001 Targeted and regulated genetic manipulation, physiological intervention to introduce biomechanical stress and injury, sophisticated measurement of cardiac function in transgenic heart at whole organ and cellular level, and the molecular/biochemical/genomic ... Full text Link to item Cite

Extracellular signal-regulated kinase plays an essential role in hypertrophic agonists, endothelin-1 and phenylephrine-induced cardiomyocyte hypertrophy.

Journal Article J Biol Chem · December 1, 2000 The extracellular signal-regulated kinase (ERK) pathway is activated by hypertrophic stimuli in cardiomyocytes. However, whether ERK plays an essential role or is implicated in all major components of cardiac hypertrophy remains controversial. Using a sele ... Full text Link to item Cite

The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes.

Journal Article FASEB J · November 2000 Activation of protein kinase C (PKC) and more recently mitogen-activated protein kinases (MAPKs) have been associated with the cardioprotective effect of ischemic preconditioning. We examined the interplay between these kinases in a characterized model of ... Full text Link to item Cite

Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest.

Journal Article Mol Cell Biol · July 2000 The p38 group of kinases belongs to the mitogen-activated protein (MAP) kinase superfamily with structural and functional characteristics distinguishable from those of the ERK, JNK (SAPK), and BMK (ERK5) kinases. Although there is a high degree of similari ... Full text Link to item Cite

High-efficiency, long-term cardiac expression of foreign genes in living mouse embryos and neonates.

Journal Article Circulation · January 18, 2000 BACKGROUND: The development of improved strategies for efficient and reproducible in vivo gene transfer into the murine heart will ultimately allow the intersection of somatic and germline gene transfer strategies to study complex features of cardiac biolo ... Full text Link to item Cite

Adenovirus technology for gene manipulation and functional studies.

Journal Article Drug Discov Today · January 2000 Recombinant adenoviral vectors are highly efficient at gene transfer in a broad spectrum of cell types and species, and have been used, both in vitro and in vivo, to achieve gain or loss of function in functional studies. In recent years, there have been s ... Full text Link to item Cite

Synergistic roles of neuregulin-1 and insulin-like growth factor-I in activation of the phosphatidylinositol 3-kinase pathway and cardiac chamber morphogenesis.

Journal Article J Biol Chem · December 24, 1999 Cardiac chamber morphogenesis requires the coordinated growth of both cardiac muscle and endocardial cell lineages. Paracrine growth factors may modulate the coordinated cellular specification and differentiation during cardiac chamber morphogenesis, as su ... Full text Link to item Cite

Calcineurin enhances acetylcholinesterase mRNA stability during C2-C12 muscle cell differentiation.

Journal Article Mol Pharmacol · November 1999 Treatment of C2-C12 mouse myoblasts with the immunosuppressant drug cyclosporin A (CsA) enhances the increase in acetylcholinesterase (AChE) expression observed during skeletal muscle differentiation. The enhanced AChE expression is due primarily to increa ... Link to item Cite

RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts.

Journal Article Mol Cell Biol · November 1999 Members of the NF-kappaB/RelB family of transcription factors play important roles in the regulation of inflammatory and immune responses. RelB, a member of this family, has been characterized as a transcription activator and is involved in the constitutiv ... Full text Link to item Cite

Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy.

Journal Article Cell · October 29, 1999 Dilated cardiomyopathy and end-stage heart failure result in multiple defects in cardiac excitation-contraction coupling. Via complementation of a genetically based mouse model of dilated cardiomyopathy, we now provide evidence that progressive chamber dil ... Full text Link to item Cite

Enhanced Galphaq signaling: a common pathway mediates cardiac hypertrophy and apoptotic heart failure.

Journal Article Proc Natl Acad Sci U S A · August 18, 1998 Receptor-mediated Gq signaling promotes hypertrophic growth of cultured neonatal rat cardiac myocytes and is postulated to transduce in vivo cardiac pressure overload hypertrophy. Although initially compensatory, hypertrophy can proceed by unknown mechanis ... Full text Link to item Cite

The low molecular weight GTPase Rho regulates myofibril formation and organization in neonatal rat ventricular myocytes. Involvement of Rho kinase.

Journal Article J Biol Chem · March 27, 1998 The assembly of contractile proteins into organized sarcomeric units is one of the most distinctive features of cardiac myocyte hypertrophy. In a well characterized in vitro model system using cultured neonatal rat ventricular myocytes, a subset of G prote ... Full text Link to item Cite

Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells.

Journal Article J Biol Chem · March 6, 1998 Activation of stress-activated protein kinases, including the p38 and the c-Jun NH2-terminal kinases (JNK), have been associated with the onset of cardiac hypertrophy and cell death in response to hemodynamic overload and ischemia/reperfusion injury. Upon ... Full text Link to item Cite

Viral sequences enable efficient and tissue-specific expression of transgenes in Xenopus.

Journal Article Nat Biotechnol · March 1998 Expression of transgenes within a single generation by direct DNA injection into vertebrate embryos has been plagued by inefficient and nonuniform gene expression. We report a novel strategy for efficient and stable expression of transgenes driven by both ... Full text Link to item Cite

Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family.

Journal Article J Biol Chem · January 23, 1998 p38 mitogen-activated protein (MAP) kinase activities were significantly increased in mouse hearts after chronic transverse aortic constriction, coincident with the onset of ventricular hypertrophy. Infection of cardiomyocytes with adenoviral vectors expre ... Full text Link to item Cite

Physiological assessment of complex cardiac phenotypes in genetically engineered mice.

Journal Article Am J Physiol · June 1997 The recent development of techniques for surgical manipulation and for the assessment of cardiac physiology in genetically engineered mice has allowed scientists to address some of the most fundamental questions related to congenital and acquired forms of ... Full text Link to item Cite

Topical application of viral vectors for epidermal gene transfer.

Journal Article J Invest Dermatol · May 1997 Efficient gene transfer with extended gene expression is essential for successful treatment of skin diseases using gene therapy. Previously we evaluated a physical gene transfer method (gene gun delivery) for its ability to transfect the epidermis in vivo. ... Full text Link to item Cite

A binding site for Pax proteins regulates expression of the gene for the neural cell adhesion molecule in the embryonic spinal cord.

Journal Article Proc Natl Acad Sci U S A · February 18, 1997 The neural cell adhesion molecule (N-CAM) mediates cell-cell interactions and is expressed in characteristic spatiotemporal patterns during development. In previous studies of factors that control N-CAM gene expression, we identified a binding site for the ... Full text Link to item Cite

Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene.

Journal Article Proc Natl Acad Sci U S A · April 30, 1996 Conditional gene expression and gene deletion are important experimental approaches for examining the functions of particular gene products in development and disease. The cre-loxP system from bacteriophage P1 has been used in transgenic animals to induce ... Full text Link to item Cite

Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites.

Journal Article Proc Natl Acad Sci U S A · March 5, 1996 During development of the vertebrate nervous system, the neural cell adhesion molecule (N-CAM) is expressed in a defined spatiotemporal pattern. We have proposed that the expression of N-CAM is controlled, in part, by proteins encoded by homeobox genes. Th ... Full text Link to item Cite

Combination gene therapy for liver metastasis of colon carcinoma in vivo.

Journal Article Proc Natl Acad Sci U S A · March 28, 1995 The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic ... Full text Link to item Cite

Functional characterization of a unique liver gene promoter.

Journal Article J Biol Chem · March 25, 1994 Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Deficiency of the PAH enzyme causes classic phenylketonuria, a common genetic disorder. The human PAH gene has a TATA-less promoter with ... Link to item Cite

Three polymorphisms but no disease-causing mutations in the proximal part of the promoter of the phenylalanine hydroxylase gene.

Journal Article Eur J Hum Genet · 1993 The proximal promoter region of the human phenylalanine hydroxylase (PAH) gene was analyzed for the presence of mutations in 122 European phenylketonuria (PKU) and hyperphenylalaninemia patients having altogether 187 uncharacterized mutant PAH alleles. Thi ... Full text Link to item Cite

Structural characterization of the 5' regions of the human phenylalanine hydroxylase gene.

Journal Article Biochemistry · September 8, 1992 Human phenylalanine hydroxylase (PAH) is expressed in a liver-specific manner and catalyzes the enzymatic conversion of phenylalanine to tyrosine. Genetic deficiency of PAH results in the autosomal-recessive disorder phenylketonuria (PKU). Through the appl ... Full text Link to item Cite

Tissue- and development-specific expression of the human phenylalanine hydroxylase/chloramphenicol acetyltransferase fusion gene in transgenic mice.

Journal Article J Biol Chem · July 25, 1992 Human phenylalanine hydroxylase (PAH) catalyzes the conversion of L-phenylalanine to L-tyrosine. Deficiency of this enzyme results in phenylketonuria, a common genetic disorder of amino acid metabolism that causes severe mental retardation. In primates, PA ... Link to item Cite