A5051551818- Heart Rate Variability and Autonomic Control
- Cardiac Ischemia and Reperfusion
- Cardiac electrophysiology and arrhythmias
- Receptor Mechanisms and Signaling
- Cardiovascular Function and Risk Factors
- Adipose Tissue and Metabolism
- Nitric Oxide and Endothelin Effects
- Cardiac Fibrosis and Remodeling
- Cardiac Imaging and Diagnostics
- Cardiomyopathy and Myosin Studies
- Cardiovascular Disease and Adiposity
- Neuropeptides and Animal Physiology
- Cardiac Arrest and Resuscitation
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Cardiovascular Health and Disease Prevention
- Genetics, Aging, and Longevity in Model Organisms
- Pharmacological Effects and Assays
- Ion channel regulation and function
- Neuroscience of respiration and sleep
- Cardiovascular Effects of Exercise
- Veterinary Pharmacology and Anesthesia
- Eicosanoids and Hypertension Pharmacology
- Cardiovascular and exercise physiology
- Anesthesia and Neurotoxicity Research
Rutgers New Jersey Medical School
2015-2025
Rutgers, The State University of New Jersey
2016-2025
Committee on Publication Ethics
2023
Vasade Biosciences (United States)
2018
UNSW Sydney
2015-2017
University of Missouri
2010-2016
New Jersey Institute of Technology
2007-2015
Molecular Cardiology and Neuromuscular Institute
2015
Victor Chang Cardiac Research Institute
2015
Harvard University
1991-2013
Silent information regulator (Sir)2, a class III histone deacetylase, mediates lifespan extension in model organisms and prevents apoptosis mammalian cells. However, beneficial functions of Sir2 remain to be shown mammals vivo at the organ level, such as heart. We addressed this issue by using transgenic mice with heart-specific overexpression Sirt1, homolog Sir2. Sirt1 was significantly upregulated (4- 8-fold) response pressure overload oxidative stress nontransgenic adult mouse hearts. Low...
The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function assessed with measurements LV systolic diastolic pressures, rate change pressure (dP/dt), dP/dt/P. Regional segment length velocity shortening. An implanted hydraulic occluder on either anterior descending or circumflex artery inflated 5- 15-min separate days. A 5-min...
Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, small-molecule, direct activator myosin. Here, show that it binds to the myosin catalytic domain and operates an allosteric mechanism transition rate into strongly actin-bound force-generating state. Paradoxically,...
MicroRNAs are posttranscriptional gene regulators that differentially expressed during various diseases and have been implicated in the underlying pathogenesis. We report here miR-199a is acutely downregulated cardiac myocytes on a decline oxygen tension. This reduction required for rapid upregulation of its target, hypoxia-inducible factor (Hif)-1alpha. Replenishing hypoxia inhibits Hif-1alpha expression stabilization p53 and, thus, reduces apoptosis. On other hand, knockdown normoxia...
We tested the hypothesis that chronically ischemic (IS) myocardium induces autophagy, a cellular degradation process responsible for turnover of unnecessary or dysfunctional organelles and cytoplasmic proteins, which could protect against consequences further ischemia. Chronically instrumented pigs were studied with repetitive myocardial ischemia produced by one, three, six episodes 90 min coronary stenosis (30% reduction in baseline flow followed reperfusion every 12 h) non-IS region as...
Decreases in regional endocardial function (ultrasonic dimension technique) and blood flow (radioactive microsphere were correlated 14 conscious dogs with acute graded levels of coronary stenosis. Coronary stenosis affected overall ventricular only slightly, but induced gradual reductions (BF) segment length (SL) shortening the ischemic zone. The relationship was best fit by an exponential relating % change SL to BF; i.e., SL(% delta) = -161.6 e -0.047BF(% (r 0.92). In segments, where no...
Increased aortic stiffness, an important feature of many vascular diseases, eg, aging, hypertension, atherosclerosis, and aneurysms, is assumed because changes in extracellular matrix (ECM).We tested the hypothesis that mechanisms also involve intrinsic stiffening smooth muscle cells (VSMCs).Stiffness was measured vitro both by atomic force microscopy (AFM) a reconstituted tissue model, using VSMCs from aorta young versus old male monkeys (Macaca fascicularis) (n=7/group), where stiffness...
The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement left ventricular pressure, dP/dt, regional wall thickening, electrograms, myocardial blood flow. Coronary occlussion reduced overall function only slightly but eliminated systolic thickening the ischemic zone flow from 1.04 +/- 0.04 to 0.27 0.02 ml/min per g endo/epi ratio 1.23 0.44 0.04, while S-T segment elevation increased 1.1 0.3 8.2 0.9 mV....
Murine models have been utilized with increasing frequency mainly due to availability of genetically engineered models. With advancement in high spatial and temporal resolution, echocardiography is used extensively for the evaluation cardiovascular function murine disease. This review summarizes general applications methods involved study mouse research, based on 20 years experience our laboratory. The goal this article provide a practical guide use echo techniques mice evaluate cardiac...
Yeast silent information regulator 2 (Sir2), a nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) and founding member of the HDAC class III family, functions in wide array cellular processes, including gene silencing, longevity, DNA damage repair. We examined whether or not mammalian ortholog Sir2 affects growth death cardiac myocytes. Cardiac myocytes express Sir2alpha predominantly nucleus. Neonatal rat were treated with 20 mmol/L (NAM), inhibitor, 50 nmol/L...
Activation of mammalian sterile 20–like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance Mst1 death caused clinically relevant pathologic stimuli unknown, however. In this study, we show that a prominent myelin basic protein activated proapoptotic cardiac myocytes and causes myocyte vitro activity–dependent manner. vivo, cardiac-specific overexpression transgenic mice results activation caspases, increased apoptosis, dilated...
Abstract To study the physiological effect of overexpression myocardial G sα (protein levels increased by approximately threefold in transgenic mice), we examined responsiveness to sympathomimetic amines echocardiography (9 MHz) five mice and control (both 10.3±0.2 months old). Myocardial contractility mice, as assessed left ventricular (LV) fractional shortening (LVFS) LV ejection fraction (LVEF), was not different from that at baseline (LVFS, 40±3% versus 36±2%; LVEF, 78±3% 74±3%). LVFS...
The effects of coronary artery reperfusion at 1 and 3 h after occlusion on infarct size (IS) in the conscious dog were compared with a second group dogs that not reperfused (24 occlusion). Infarct was calculated from creatine kinase (CK) appearing blood samples (IS(s)) myocardial CK depletion (IS(m)), determined gross histological inspection pathological tissue (IS(p)). Under both conditions, IS(m) correlated well IS(p). In 24-h occlusions, IS(s) (IS(s) = 14.26 + 1.18 x IS(m), r 0.92). dogs,...
We examined the mechanism of atrial natriuretic factor (ANF) transcription by isoproterenol (ISO), an agonist for β-adrenergic receptor (βAR), in cardiac myocytes. ISO only modestly activated members mitogen-activated protein kinase family. ISO-induced ANF was not affected inhibition kinases, whereas it significantly inhibited KN93, inhibitor Ca<sup>2+</sup>/calmodulin-dependent (CaM II). Production 3′-phosphorylated phosphatidylinositides (3 phosphoinositides) also required transcription....
Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall mechanisms is unknown any organs. We generated transgenic mice with cardiac-specific overexpression a dominant negative (DN) mutant (C32S/C35S) (Tg-DN-Trx1 mice), which activity endogenous Trx was diminished. Markers oxidative stress were significantly increased hearts from Tg-DN-Trx1 compared those nontransgenic (NTg) mice. exhibited cardiac...
Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall mechanisms is unknown any organs. We generated transgenic mice with cardiac-specific overexpression a dominant negative (DN) mutant (C32S/C35S) (Tg-DN-Trx1 mice), which activity endogenous Trx was diminished. Markers oxidative stress were significantly increased hearts from Tg-DN-Trx1 compared those nontransgenic (NTg) mice. exhibited cardiac...
The major goal of this study was to determine whether impaired myocardial contractile function during the development progressive coronary artery stenosis induced by ameroid constriction in conscious pigs reflected "hibernation" or "stunning." Minipigs were instrumented with a constrictor and hydraulic occluder, regional wall thickness crystals, left ventricular (LV) pressure gauge, aortic atrial catheters. In seven which it measured, systolic thickening (WT) distal fell maximum 56 +/- 6% at...
Inactivation of glycogen synthase kinase 3β (GSK3β) is critical for transcription atrial natriuretic factor (ANF) by β-adrenergic receptors in cardiac myocytes. We examined the mechanism which GSK3β regulates ANF transcription. Stimulation induced nuclear accumulation GATA4, whereas was suppressed dominant negative suggesting that GATA4 plays an important role Interestingly, GATA4-mediated markedly attenuated GSK3β. physically associates with and phosphorylates <i>in vitro</i>....
To seek evidence that the nonhuman primate arterial wall, as it ages in absence of atherosclerosis, exhibits alterations pathways are involved pathogenesis experimental we assessed aortic matrix metalloproteinase-2 (MMP-2) and its regulators, ie, membrane type-1 metalloproteinase (MT1-MMP) tissue inhibitor (TIMP-2), expression angiotensin II (Ang II), angiotensin-converting enzyme (ACE), chymase young (6.4+/-0.7 years) old (20.0+/-1.9 male monkeys. With advancing age, (1) intimal thickness...
The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared that a group normal dogs. Cardiac were produced by tricuspid avulsion progressive pulmonary stenosis. sensitivity to transient hypertension assessed determining slope regression line relating prolongation R-R interval rise systolic arterial pressure during elevation induced an intravenous injection 1-phenylephrine. mean averaged 22.4+/-2.3 msec/nm Hg 16 animals....