Scholars@Duke
Lan Mao

Lan Mao

Assistant Professor Emeritus in Medicine
Medicine, Cardiology
mao00004@mc.duke.edu
Duke Box 3104, Durham, NC 27710
231 Clin Res Lab Bldg, Durham, NC 27710

Selected Publications

Characterization of cardiovascular injury in mice following partial-heart irradiation with clinically relevant dose and fractionation.

Journal Article Radiother Oncol · April 2021 BACKGROUND AND PURPOSE: Late cardiac toxicity is a major side effect of radiation therapy (RT) for breast cancer. We developed and characterized a mouse model of radiation-induced heart disease that mimics the dose, fractionation, and beam arrangement of l ... Full text Link to item Cite

The β-arrestin-biased β-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility.

Journal Article Proc Natl Acad Sci U S A · June 2, 2020 A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and incr ... Full text Open Access Link to item Cite

Lack of Thy1 defines a pathogenic fraction of cardiac fibroblasts in heart failure.

Journal Article Biomaterials · April 2020 In response to heart injury, inflammation, or mechanical overload, quiescent cardiac fibroblasts (CFs) can become activated myofibroblasts leading to pathological matrix remodeling and decline in cardiac function. Specific targeting of fibroblasts may thus ... Full text Link to item Cite

A murine model of increased coronary sinus pressure induces myocardial edema with cardiac lymphatic dilation and fibrosis.

Journal Article Am J Physiol Heart Circ Physiol · April 1, 2020 Myocardial edema is a consequence of many cardiovascular stressors, including myocardial infarction, cardiac bypass surgery, and hypertension. The aim of this study was to establish a murine model of myocardial edema and elucidate the response of cardiac l ... Full text Link to item Cite

Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.

Journal Article J Immunol · March 15, 2020 An increasing body of evidence suggests that bone marrow-derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a sp ... Full text Link to item Cite

The deubiquitinase ubiquitin-specific protease 20 is a positive modulator of myocardial β1-adrenergic receptor expression and signaling.

Journal Article J Biol Chem · February 15, 2019 Reversible ubiquitination of G protein-coupled receptors regulates their trafficking and signaling; whether deubiquitinases regulate myocardial β1-adrenergic receptors (β1ARs) is unknown. We report that ubiquitin-specific protease 20 (USP20) deubiquitinate ... Full text Link to item Cite

A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling.

Journal Article J Endocr Soc · February 1, 2019 Progesterone is primarily a pregnancy-related hormone, produced in substantial quantities after ovulation and during gestation. Traditionally known to function via nuclear receptors for transcriptional regulation, there is also evidence of nonnuclear actio ... Full text Open Access Link to item Cite

β-arrestin 1 regulates β2-adrenergic receptor-mediated skeletal muscle hypertrophy and contractility.

Journal Article Skelet Muscle · December 27, 2018 BACKGROUND: β2-adrenergic receptors (β2ARs) are the target of catecholamines and play fundamental roles in cardiovascular, pulmonary, and skeletal muscle physiology. An important action of β2AR stimulation on skeletal muscle is anabolic growth, which has l ... Full text Open Access Link to item Cite

The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction.

Journal Article J Clin Invest · November 1, 2018 Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critica ... Full text Link to item Cite

Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2.

Journal Article Synapse · January 2018 The "brain-gut" peptide ghrelin, which mediates food-seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein-coupled receptor GHSR1a, and administration of ghrelin increases the rewardi ... Full text Link to item Cite

Sirtuin 5 is required for mouse survival in response to cardiac pressure overload.

Journal Article J Biol Chem · December 1, 2017 In mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase that controls several metabolic pathways. Although a wide range of SIRT5 targets have been identified, the overall function of SIRT5 in organismal metabolic homeostasis remains uncle ... Full text Link to item Cite

Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.

Journal Article JCI Insight · September 7, 2017 The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic receptor (βAR) signaling and endocytosis. Previous studies showed that cardi ... Full text Open Access Link to item Cite

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich's ataxia cardiomyopathy model.

Journal Article JCI Insight · July 20, 2017 Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which ... Full text Link to item Cite

Inducible Fgf13 ablation enhances caveolae-mediated cardioprotection during cardiac pressure overload.

Journal Article Proc Natl Acad Sci U S A · May 16, 2017 The fibroblast growth factor (FGF) homologous factor FGF13, a noncanonical FGF, has been best characterized as a voltage-gated Na+ channel auxiliary subunit. Other cellular functions have been suggested, but not explored. In inducible, cardiac-specific Fgf ... Full text Link to item Cite

β-Arrestin mediates the Frank-Starling mechanism of cardiac contractility.

Journal Article Proc Natl Acad Sci U S A · December 13, 2016 The Frank-Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank-Starling relati ... Full text Link to item Cite

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension.

Journal Article J Vis Exp · April 11, 2016 Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, ... Full text Link to item Cite

Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization.

Journal Article Mol Endocrinol · April 2016 Oxytocin is a potent uterotonic agent and is used clinically for induction and augmentation of labor, as well as for prevention and treatment of postpartum hemorrhage. Oxytocin increases uterine contractility by activating the oxytocin receptor (OXTR), a m ... Full text Link to item Cite

The role of β-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome.

Journal Article Am J Physiol Heart Circ Physiol · November 2015 Ang II type 1a receptor (AT1aR)-mediated activation of MAPKs contributes to thoracic aortic aneurysm (TAA) development in Marfan syndrome (MFS). β-Arrestin2 (βarr2) is known to mediate AT1aR-dependent MAPK activation, as well as proproliferative and profib ... Full text Link to item Cite

Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

Journal Article Cell Rep · October 20, 2015 Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and us ... Full text Link to item Cite

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice.

Journal Article J Vis Exp · September 17, 2015 Cardiac pressure-volume loop analysis is the "gold-standard" in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examina ... Full text Link to item Cite

Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors.

Journal Article Circulation · June 16, 2015 BACKGROUND: Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin ... Full text Link to item Cite

Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium.

Journal Article J Clin Invest · August 2014 Cells isolated from patients with ataxia telangiectasia are exquisitely sensitive to ionizing radiation. Kinase inhibitors of ATM, the gene mutated in ataxia telangiectasia, can sensitize tumor cells to radiation therapy, but concern that inhibiting ATM in ... Full text Link to item Cite

β-arrestin1-biased β1-adrenergic receptor signaling regulates microRNA processing.

Journal Article Circ Res · February 28, 2014 RATIONALE: MicroRNAs (miRs) are small, noncoding RNAs that function to post-transcriptionally regulate gene expression. First transcribed as long primary miR transcripts (pri-miRs), they are enzymatically processed in the nucleus by Drosha into hairpin int ... Full text Open Access Link to item Cite

Normal cardiac function in mice with supraphysiological cardiac creatine levels.

Journal Article Am J Physiol Heart Circ Physiol · February 2014 Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine c ... Full text Link to item Cite

Anatomical and functional imaging of myocardial infarction in mice using micro-CT and eXIA 160 contrast agent.

Journal Article Contrast Media Mol Imaging · 2014 Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro-CT cardiac ... Full text Link to item Cite

CCR2 deficiency, dysregulation of Notch signaling, and spontaneous pulmonary arterial hypertension.

Journal Article Am J Respir Cell Mol Biol · May 2013 In pulmonary arterial hypertension (PAH), there is overexpression of the chemokine, C-C chemokine ligand type 2 (CCL2), and infiltration of myeloid cells into the pulmonary vasculature. Inhibition of CCL2 in animals decreases PAH, suggesting that the CCL2 ... Full text Link to item Cite

Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction.

Journal Article J Mol Cell Cardiol · January 2013 Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase whose biological function remains largely unknown. We have recently shown that TNNI3K expression greatly accelerates cardiac dysfunction in mouse models of cardiomyopathy, indicati ... Full text Link to item Cite

beta-arrestin1 Stimulates the Processing of a Subset of MicroRNAs

Conference CIRCULATION RESEARCH · December 1, 2012 Link to item Cite

β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury.

Journal Article Am J Physiol Heart Circ Physiol · October 15, 2012 Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biase ... Full text Link to item Cite

p53 functions in endothelial cells to prevent radiation-induced myocardial injury in mice.

Journal Article Sci Signal · July 24, 2012 Radiation therapy, which is used for the treatment of some cancers, can cause delayed heart damage. In the heart, p53 influences myocardial injury that occurs after multiple types of stress. Here, we demonstrated that p53 functioned in endothelial cells to ... Full text Link to item Cite

X-linked inhibitor of apoptosis protein-mediated attenuation of apoptosis, using a novel cardiac-enhanced adeno-associated viral vector.

Journal Article Hum Gene Ther · June 2012 Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory ha ... Full text Link to item Cite

Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.

Journal Article PLoS One · 2012 Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diab ... Full text Link to item Cite

β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration.

Journal Article Am J Physiol Endocrinol Metab · March 2011 Desensitization of the oxytocin receptor (OXTR) in the setting of prolonged oxytocin exposure may lead to dysfunctional labor, which increases the risk for cesarean delivery, and uterine atony, which may result in postpartum hemorrhage. The molecular mecha ... Full text Link to item Cite

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

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

TRPC1 channels are critical for hypertrophic signaling in the heart.

Journal Article Circ Res · November 6, 2009 RATIONALE: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein-coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel acti ... Full text Link to item Cite

Beta1-adrenergic receptors stimulate cardiac contractility and CaMKII activation in vivo and enhance cardiac dysfunction following myocardial infarction.

Journal Article Am J Physiol Heart Circ Physiol · October 2009 The beta-adrenergic receptor (betaAR) signaling system is one of the most powerful regulators of cardiac function and a key regulator of Ca(2+) homeostasis. We investigated the role of betaAR stimulation in augmenting cardiac function and its role in the a ... Full text Link to item Cite

Tnni3k modifies disease progression in murine models of cardiomyopathy.

Journal Article PLoS Genet · September 2009 The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (car ... Full text Link to item Cite

A role for the thromboxane receptor in L-NAME hypertension.

Journal Article Am J Physiol Renal Physiol · October 2008 Actions of the lipid mediator thromboxane (Tx) A2 acting through the TP receptor contribute to the pathogenesis of cardiovascular disease. To further explore the role of TxA2 in hypertension, we examined the consequences of deficiency of the TP receptor on ... Full text Link to item Cite

Discordant on/off switching of gene expression in myocytes during cardiac hypertrophy in vivo.

Journal Article Proc Natl Acad Sci U S A · September 2, 2008 To determine whether the expression of cardiac genes changes in a graded manner or by on/off switching when cardiac myocytes change genetic programs in living animals, we have studied two indicator genes that change their expression oppositely in mouse bin ... Full text Link to item Cite

Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice.

Journal Article Am J Physiol Gastrointest Liver Physiol · June 2008 Reduced sinusoidal endothelial nitric oxide (NO) production contributes to increased intrahepatic resistance and portal hypertension after liver injury. We hypothesized that V-PYRRO/NO, an NO donor prodrug metabolized "specifically" in the liver, would red ... Full text Link to item Cite

Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G alpha o* protein.

Journal Article Am J Physiol Heart Circ Physiol · March 2008 In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of G o is still poorly defined. To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a c ... Full text Link to item Cite

Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8.

Journal Article Basic Res Cardiol · January 2008 OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms le ... Full text Link to item Cite

Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice.

Journal Article Am J Pathol · February 2007 The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional sh ... Full text Link to item Cite

Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice.

Journal Article Mol Imaging · 2007 The purpose of this study was to investigate the use of micro-computed tomography (micro-CT) for morphological and functional phenotyping of muscle LIM protein (MLP) null mice and to compare micro-CT with M-mode echocardiography. MLP null mice and controls ... Link to item Cite

Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling.

Journal Article Am J Physiol Heart Circ Physiol · October 2006 Adverse remodeling after myocardial infarction (MI) determines the progression of heart failure. Failing hearts are characterized by downregulation of beta-adrenergic receptor (beta-AR) signaling in part because of increased beta-AR kinase 1 activity. Our ... Full text Link to item Cite

Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice.

Journal Article J Clin Invest · August 2006 The carboxypeptidase ACE2 is a homologue of angiotensin-converting enzyme (ACE). To clarify the physiological roles of ACE2, we generated mice with targeted disruption of the Ace2 gene. ACE2-deficient mice were viable, fertile, and lacked any gross structu ... Full text Link to item Cite

Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction.

Journal Article J Clin Invest · June 2006 For over a century, there has been intense debate as to the reason why some cardiac stresses are pathological and others are physiological. One long-standing theory is that physiological overloads such as exercise are intermittent, while pathological overl ... Full text Link to item Cite

NSAIDs and cardiovascular risk - Reply [2]

Journal Article Cell Metabolism · December 1, 2005 Full text Cite

Prostacyclin protects against elevated blood pressure and cardiac fibrosis.

Journal Article Cell Metab · September 2005 Specific inhibitors of COX-2 have been associated with increased risk for cardiovascular complications. These agents reduce prostacyclin (PGI2) without affecting production of thromboxane (Tx) A2. While this abnormal pattern of eicosanoid generation has be ... Full text Link to item Cite

An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation.

Journal Article Proc Natl Acad Sci U S A · August 23, 2005 The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiov ... Full text Link to item Cite

cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.

Journal Article Am J Physiol Heart Circ Physiol · March 2005 Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease state ... Full text Link to item Cite

Estrogen receptor-beta mediates male-female differences in the development of pressure overload hypertrophy.

Journal Article Am J Physiol Heart Circ Physiol · February 2005 The goal of this study was to determine the role of estrogen receptor subtypes in the development of pressure overload hypertrophy in mice. Epidemiological studies have suggested gender differences in the development of hypertrophy and heart disease, but t ... Full text Link to item Cite

Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway.

Journal Article Circ Res · September 3, 2004 Human CYP2J2 is abundant in heart and active in the biosynthesis of epoxyeicosatrienoic acids (EETs); however, the functional role of this P450 and its eicosanoid products in the heart remains unknown. Transgenic mice with cardiomyocyte-specific overexpres ... Full text Link to item Cite

Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene.

Journal Article Proc Natl Acad Sci U S A · March 2, 2004 Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II ... Full text Link to item Cite

Role for thromboxane receptors in angiotensin-II-induced hypertension.

Journal Article Hypertension · February 2004 To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension. To determine whether genetic background might alter the phys ... Full text Link to item Cite

Inhibition of receptor-localized PI3K preserves cardiac beta-adrenergic receptor function and ameliorates pressure overload heart failure.

Journal Article J Clin Invest · October 2003 beta-Adrenergic receptor (betaAR) downregulation and desensitization are hallmarks of the failing heart. However, whether abnormalities in betaAR function are mechanistically linked to the cause of heart failure is not known. We hypothesized that downregul ... Full text Link to item Cite

Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance.

Journal Article J Biol Chem · September 5, 2003 S100A1, a Ca2+-sensing protein of the EF-hand family, is most highly expressed in myocardial tissue, and cardiac S100A1 overexpression in vitro has been shown to enhance myocyte contractile properties. To study the physiological consequences of S100A1 in v ... Full text Link to item Cite

Pressure overload selectively up-regulates Ca2+/calmodulin-dependent protein kinase II in vivo.

Journal Article Mol Endocrinol · February 2003 Signals transduced by the multifunctional calcium/calmodulin-dependent protein kinases (CaMKs), have been suggested to regulate the development of hypertrophy. We address the role of the three multifunctional CaMKs, CaMK I, II, and IV, in this process usin ... Full text Link to item Cite

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy.

Journal Article Am J Physiol Heart Circ Physiol · June 2002 Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (sigma)-strain (epsi ... Full text Link to item Cite

Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice.

Journal Article Circulation · November 13, 2001 BACKGROUND: Stimulation of beta(1)- and beta(2)-adrenergic receptors (ARs) in the heart results in positive inotropy. In contrast, it has been reported that the beta(3)AR is also expressed in the human heart and that its stimulation leads to negative inotr ... Full text Open Access Link to item Cite

Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure-overload cardiac hypertrophy.

Journal Article J Am Coll Cardiol · September 2001 OBJECTIVES: We sought to define the role of norepinephrine and epinephrine in the development of cardiac hypertrophy and to determine whether the absence of circulating catecholamines alters the activation of downstream myocardial signaling pathways. BACKG ... Full text Link to item Cite

Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice.

Journal Article J Clin Invest · April 2001 Mice lacking natriuretic peptide receptor A (NPRA) have marked cardiac hypertrophy and chamber dilatation disproportionate to their increased blood pressure (BP), suggesting, in support of previous in vitro data, that the NPRA system moderates the cardiac ... Full text Link to item Cite

Cardiac overexpression of a G(q) inhibitor blocks induction of extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase activity in in vivo pressure overload.

Journal Article Circulation · March 13, 2001 BACKGROUND: Understanding the cellular signals that initiate cardiac hypertrophy is of critical importance in identifying the pathways that mediate heart failure. The family of mitogen-activated protein kinases (MAPKs), including the extracellular signal-r ... Full text Link to item Cite

Cellular and functional defects in a mouse model of heart failure.

Journal Article Am J Physiol Heart Circ Physiol · December 2000 Heart failure and dilated cardiomyopathy develop in mice that lack the muscle LIM protein (MLP) gene (MLP(-/-)). The character and extent of the heart failure that occurs in MLP(-/-) mice were investigated using echocardiography and in vivo pressure-volume ... Full text Link to item Cite

Physiological induction of a beta-adrenergic receptor kinase inhibitor transgene preserves ss-adrenergic responsiveness in pressure-overload cardiac hypertrophy.

Journal Article Circulation · November 28, 2000 BACKGROUND: Transgenic mice with constitutive myocardium-targeted expression of a peptide inhibitor of the ss-adrenergic receptor kinase (ssARKct) have increased in vivo cardiac function and enhanced ss-adrenergic receptor (ssAR) responsiveness. METHODS AN ... Full text Link to item Cite

Sustained expression of human factor VIII in mice using a parvovirus-based vector.

Journal Article Blood · March 1, 2000 Persistent therapeutic levels of human factor VIII (hFVIII) would signify a major advance in the treatment of hemophilia A. Here we report sustained expression of hFVIII in immunocompetent mice using recombinant adeno-associated virus (rAAV) vectors. AAV c ... Link to item Cite

Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy.

Journal Article J Biol Chem · February 18, 2000 Activation of phosphoinositide 3-kinases is coupled to both phosphotyrosine/growth factor and G protein-coupled receptors. We explored the role of phosphoinositide 3-kinase activation in myocardium during in vivo pressure overload hypertrophy in mice. Cyto ... Full text Link to item Cite

Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.

Journal Article Circulation · October 19, 1999 BACKGROUND: Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases o ... Full text Link to item Cite

Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction.

Journal Article J Card Fail · September 1998 BACKGROUND: Recombinant human growth hormone (rhGH) has shown beneficial effects on cardiac function after myocardial infarction (MI) in rats. High-dose angiotensin II (AT1) receptor blockade in normal rats inhibited the hypertrophic effect of growth hormo ... Full text Link to item Cite

Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice.

Journal Article Am J Physiol · August 1998 Cardiac hypertrophic and contractile responses were studied in mice administered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg . kg-1 . day-1), alone or in combination (IGF-I/GH), for 2 wk. Also, changes in expression of selected left ve ... Full text Link to item Cite

Force-frequency effect is a powerful determinant of myocardial contractility in the mouse

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · December 1, 1997 The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR %vas first slowed with a sinus node inhibitor (zatebradine), a ... Cite

Left ventricular volumes and function in the embryonic mouse heart.

Journal Article Am J Physiol · September 1997 This study describes miniaturized technology for the in vivo analysis of the volume and function of the embryonic mouse heart and the application of this technology to study the normal embryonic left ventricle (LV) at two stages of development. With the us ... Full text Link to item Cite

Force-frequency effect is a powerful determinant of myocardial contractility in the mouse.

Journal Article Am J Physiol · September 1997 The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR was first slowed with a sinus node inhibitor (zatebradine), an ... Full text Link to item Cite

Force-frequency relations in the failing rabbit heart and responses to adrenergic stimulation.

Journal Article J Card Fail · March 1997 BACKGROUND: Recent experiments have documented the importance of beta-adrenergic regulation of the force-frequency relation (FFR) in the normal and failing heart. As in isolated human cardiac muscle, a descending limb of the FFR occurs at high frequencies ... Full text Link to item Cite

Transthoracic echocardiography in models of cardiac disease in the mouse.

Journal Article Circulation · September 1, 1996 BACKGROUND: Transthoracic echocardiography (M-mode and Doppler) offers a noninvasive approach for in vivo evaluation of the mouse heart. The present study examines its usefulness for assessing the morphological/functional phenotype of the left ventricle (L ... Full text Link to item Cite

Enhanced myocardial relaxation in vivo in transgenic mice overexpressing the beta2-adrenergic receptor is associated with reduced phospholamban protein.

Journal Article J Clin Invest · April 1, 1996 To assess the effect of targeted myocardial beta-adrenergic receptor (AR) stimulation on relaxation and phospholamban regulation, we studied the physiological and biochemical alterations associated with overexpression of the human beta2-AR gene in transgen ... Full text Open Access Link to item Cite

Effects of induced tolerance to bacterial lipopolysaccharide on myocardial infarct size in rats.

Journal Article Cardiovasc Res · January 1996 OBJECTIVES: Induced tolerance to bacterial lipopolysaccharide (LPS) by pretreatment with sublethal doses of LPS has been shown to reduce the inflammatory response of monocytes, circulating PMNs and PMN adhesion to endothelial cells in response to subsequen ... Link to item Cite

ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice.

Journal Article Am J Physiol · June 1994 There is increasing evidence that the renin-angiotensin system may play a important role in cardiac hypertrophy. To assess the role of angiotensin II in the induction of cardiac hypertrophy, three groups of adult mice were subjected to left ventricular pre ... Full text Link to item Cite

In vivo assessment of left ventricular remodelling after myocardial infarction by digital video contrast angiography in the rat.

Journal Article Cardiovasc Res · March 1994 OBJECTIVE: The aim was to develop a digital video contrast angiographic method for assessing global left ventricular function and volume in vivo in the rat and then to apply it to a study of ventricular remodelling after coronary occlusion, with and withou ... Full text Link to item Cite