A5038486715- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Cardiac electrophysiology and arrhythmias
- Pluripotent Stem Cells Research
- Cardiac Fibrosis and Remodeling
- Cardiovascular Disease and Adiposity
- Cardiac Valve Diseases and Treatments
- Cardiac Structural Anomalies and Repair
- Cardiac Imaging and Diagnostics
- Metabolism, Diabetes, and Cancer
- Growth Hormone and Insulin-like Growth Factors
- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Heart Failure Treatment and Management
- Viral Infections and Immunology Research
- GDF15 and Related Biomarkers
- Mesenchymal stem cell research
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Birth, Development, and Health
University of Miami
2016-2025
Midwest Institute for Minimally Invasive Therapies
2020-2022
Miami Transplant Institute
2010-2014
Stem Cell Institute
2014
Universidade Federal de São Paulo
2000-2007
Fundação de Apoio à Universidade Federal de São Paulo
2004
Significance A high-resolution genetic lineage-tracing study in mice reveals that cKit identifies multipotent progenitors of cardiac neural crest (CNC) origin. Normally, the proportion cardiomyocytes produced from this lineage is limited, not because poor differentiation capacity as previously thought, but stage-specific changes activity bone morphogenetic protein pathway. Transient antagonism efficiently directs mouse iPSCs toward CNC and, consequently, generation + CNCs with full to form...
Whether the growth hormone (GH)/insulin-like factor 1(IGF-1) axis exerts cardioprotective effects remains controversial; and underlying mechanism(s) for such actions are unclear. Here we tested hypothesis that hormone-releasing (GHRH) directly activates cellular reparative mechanisms within injured heart, in a GH/IGF-1 independent fashion. After experimental myocardial infarction (MI), rats were randomly assigned to receive, during 4-week period, either placebo (n = 14), rat recombinant GH...
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory (RLC) cardiac myosin is known to play a beneficial role in heart disease, but idea phosphorylation-mediated reversal hypertrophic cardiomyopathy (HCM) phenotype novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that D166V (Aspartate166 → Valine) mutation-induced changes morphology and function coincided with largely reduced RLC situ. We hypothesized introduction constitutively phosphorylated...
Both cardiac myocytes and stem cells (CSCs) express the receptor of growth hormone releasing (GHRH), activation which improves injury responses after myocardial infarction (MI). Here we show that a GHRH-agonist (GHRH-A; JI-38) reverses ventricular remodeling enhances functional recovery in setting chronic MI. This response is mediated entirely by GHRH (GHRHR), as demonstrated use highly selective antagonist (MIA-602). One month MI, animals were randomly assigned to receive: placebo, GHRH-A...
To test the hypothesis that activation of growth hormone-releasing hormone (GHRH) receptor signalling pathway within myocardium both prevents and reverses diastolic dysfunction pathophysiologic features consistent with heart failure preserved ejection fraction (HFpEF). Impaired myocardial relaxation, fibrosis, ventricular stiffness, among other multi-organ morbidities, characterize phenotype underlying HFpEF syndrome. Despite rapidly increasing prevalence HFpEF, few effective therapies have...
Abstract We investigated the impact of phosphomimetic (Ser15 → Asp15) myosin regulatory light chain (S15D‐RLC) on Super‐Relaxed (SRX) state using previously characterized transgenic (Tg) S15D‐D166V rescue mice, comparing them to Hypertrophic Cardiomyopathy (HCM) Tg‐D166V model and wild‐type (WT) RLC mice. In model, we observed a disruption SRX state, resulting in transition from DRX (Disordered Relaxed) which explains hypercontractility D166V‐mutated motors. The presence S15D moiety...
Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the size, and evaluate anatomic functional variables of left ventricle. Myocardial infarction produced 43 female Wistar rats by ligature coronary artery. Echocardiography performed 5 weeks later measure ventricular diameter transverse area (mean 3 planes), size (percentage arc with on systolic function change fractional area,...
Aldosterone receptor antagonism reduces mortality and improves post-myocardial infarction (MI) remodeling. Because aldosterone estrogen signaling pathways interact, we hypothesized that blockade is sex-specific. Therefore, investigated the impact of eplerenone on left ventricular (LV) remodeling gene expression male infarcted rats versus female rats. MI Sham animals were randomized to receive (100 mg/kg/day) or placebo 3 days post-surgery for 4 weeks assessed by echocardiography. In group,...
Mammalian heart regenerative activity is lost before adulthood but increases after cardiac injury. Cardiac repair mechanisms, which involve both endogenous stem cells (CSCs) and cardiomyocyte cell-cycle reentry, are inadequate to achieve full recovery myocardial infarction (MI). Mice deficient in S-nitrosoglutathione reductase (GSNOR(-⁄-)), an enzyme regulating S-nitrosothiol turnover, have preserved function MI. Here, we tested the hypothesis that GSNOR modulates cell proliferation post-MI...
Significance Stem cell therapy is an emerging approach to the treatment of heart failure. Endogenous or transplanted stem cells have limited repair capacity due damage by exposure stress. Agonists growth hormone-releasing hormone receptor (GHRH-R) been previously shown increase number endogenous cardiac (CSCs) after myocardial infarction; enhance vasculogenesis mesenchymal cells; and improve growth, engraftment, survival pancreatic islets in experimental models. This study shows that CSCs...
The presence of tissue specific precursor cells is an emerging concept in organ formation and homeostasis. Several progenitors are described the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify neonatal kidney-derived c-kit(+) population that fulfills all criteria cell. These were found thick ascending limb Henle's loop exhibited clonogenicity, self-renewal, multipotentiality with differentiation capacity into mesoderm ectoderm progeny. Additionally,...
Background Growth hormone–releasing hormone agonists ( GHRH ‐As) stimulate cardiac repair following myocardial infarction MI ) in rats through the activation of signaling pathway within heart. We tested hypothesis that administration ‐As prevents ventricular remodeling a swine subacute model. Methods and Results Twelve female Yorkshire (25 to 30 kg) underwent transient occlusion left anterior descending coronary artery ). Two weeks post , were randomized receive injections either μg/kg ‐A MR...
In the current preclinical study, we demonstrate therapeutic potential of sarcospan (SSPN) overexpression to alleviate cardiomyopathy associated with Duchenne muscular dystrophy (DMD) utilizing dystrophin-deficient mdx mice utrophin haploinsufficiency that more accurately represent severe disease course human DMD. SSPN interacts dystrophin, DMD gene product, and its autosomal paralog utrophin, which is upregulated in as a partial compensatory mechanism. transgenic have enhanced abundance...
Abstract Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis fibrosis. Here we test the hypothesis decreased cord levels in preterm predict increased BPD–PH risk early supplementation prevents BPD-like phenotype PH rodents exposed to neonatal hyperoxia. In experiment 1, were measured blood of who enrolled a longitudinal cohort...
This randomized study used rigorous hemodynamic tools to test the efficacy of a synthetic GHRH agonist improve cardiac performance in cardiometabolic HFpEF. Daily injection agonist, MR-356, reduced HFpEF-like effects as evidenced by improved diastolic dysfunction, hypertrophy, fibrosis, and pulmonary congestion. Notably, end-diastolic pressure pressure-volume relationship were reset control levels. Moreover, treatment with MR-356 increased exercise capacity myocardial stress associated...
The E143K (Glu → Lys) mutation in the myosin essential light chain has been associated with restrictive cardiomyopathy (RCM) humans, but mechanisms that underlie development of defective cardiac function are unknown. Using transgenic E143K-RCM mice, we sought to determine molecular and cellular triggers E143K-induced heart remodelling.The abnormalities morphology observed by echocardiography invasive haemodynamics were paralleled augmented active passive tension measured skinned papillary...
// Rosemeire M. Kanashiro-Takeuchi 1, 2, * , Luca Szalontay 3, Andrew V. Schally 4, 5, 6 Lauro Takeuchi 1 Petra Popovics 7, 8 Miklos Jaszberenyi 4 Irving Vidaurre 3 Marta Zarandi Ren-Zhi Cai Norman L. Block Joshua Hare Ferenc G. Rick 9 Interdisciplinary Stem Cell Institute, University of Miami, Miller School Medicine, Florida, United States America 2 Department Molecular and Cellular Pharmacology, Veterans Affairs Medical Center South Florida Foundation for Research Education, Pathology, 5...
Significance This randomized, blinded study used rigorous hemodynamic tools to test the efficacy of a synthetic growth hormone-releasing hormone agonist (GHRH‐A) on restoration diastolic function in large animal model chronic kidney disease (CKD)-induced heart failure with preserved ejection fraction (HFpEF). CKD was produced Yorkshire swine by performing 5/6 nephrectomy via catheter-based renal artery embolization. HFpEF evident at 12 wk postembolization. Daily injection GHRH-A improved...
Background Preeclampsia, a leading cause of maternal and fetal mortality morbidity, is characterized by an increase in S-nitrosylated proteins reactive oxygen species, suggesting pathophysiologic role for dysregulation nitrosylation nitrosative stress. Methods Results Here, we show that mice lacking S-nitrosoglutathione reductase (
Kidney-derived c-kit+ cells exhibit progenitor/stem cell properties and can regenerate epithelial tubular following ischemia-reperfusion injury in rats. We therefore investigated whether contribute to podocyte repair a rat model of acute proteinuria induced by puromycin aminonucleoside (PAN), the experimental prototype human minimal change disease early stages focal segmental glomerulosclerosis. found that accelerated kidney recovery improving foot process effacement (foot width was lower...