A5032748291- Receptor Mechanisms and Signaling
- Hormonal Regulation and Hypertension
- Cardiac electrophysiology and arrhythmias
- Renin-Angiotensin System Studies
- Neuropeptides and Animal Physiology
- Ion channel regulation and function
- Pharmacological Effects and Assays
- Protein Kinase Regulation and GTPase Signaling
- Eicosanoids and Hypertension Pharmacology
- Diabetes Treatment and Management
- Nitric Oxide and Endothelin Effects
- Heart Failure Treatment and Management
- Adipose Tissue and Metabolism
- Heart Rate Variability and Autonomic Control
- Cardiac Ischemia and Reperfusion
- Apelin-related biomedical research
- Estrogen and related hormone effects
- Phosphodiesterase function and regulation
- ATP Synthase and ATPases Research
- Cardiac Fibrosis and Remodeling
- Pharmacogenetics and Drug Metabolism
- Neuroscience and Neuropharmacology Research
- Computational Drug Discovery Methods
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Pharmacological Receptor Mechanisms and Effects
Nova Southeastern University
2015-2024
University of Fort Lauderdale
2024
South University
2023
Southeastern University
2021
AdventHealth Orlando
2020
Regional Medical Center
2020
University of Miami Hospital
2020
Stamatopoulos and Associates (Greece)
2006-2019
GTx (United States)
2018
Temple University
2013-2017
Background— The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute dysfunctional β-adrenergic (βAR) signaling and cardiac function. peptide βARKct, which can inhibit the activation improve βAR signaling, has been shown transgenic models short-term gene transfer experiments rescue heart failure (HF). This study was designed evaluate long-term βARKct expression HF with use stable myocardial delivery adeno-associated virus serotype 6 (AAV6). Methods...
Aldosterone produces a multitude of effects in vivo, including promotion postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation AngII type 1 receptors (AT(1)Rs). Until now, general consensus for signaling to aldosterone production has been that it proceeds via G(q/11)-proteins, which AT(1)R normally couples. Here, we describe novel pathway underlying...
β-Arrestin (βarr)-1 and β-arrestin-2 (βarrs) are universal G-protein-coupled receptor adapter proteins that negatively regulate cardiac β-adrenergic (βAR) function via βAR desensitization downregulation. In addition, they mediate G-protein-independent signaling, which might be beneficial, for example, antiapoptotic, the heart. However, specific role(s) of each βarr isoform in dysfunction, molecular hallmark chronic heart failure (HF), remains unknown. Furthermore, adrenal βarr1 exacerbates...
Heart failure is the leading cause of death in Western world, and new innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 βarr-2 functionally distinct heart. βarr1 cardiotoxic, decreasing contractility by opposing β1AR (adrenergic signaling promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits post-MI but its effects on cardiac function not well understood. Herein, we sought to investigate whether...
Introduction: Nicotine is a major component of cigarette smoke with various detrimental cardiovascular effects, including increased oxidative stress in the heart. Agonism α 2 -adrenergic receptors (ARs), such as dexmedetomidine, has been documented to exert cardioprotective effects against and related apoptosis necroptosis. -ARs are membrane-residing G protein-coupled (GPCRs) that primarily activate Gi/o proteins. They also subjected GPCR-kinase (GRK)-2-dependent desensitization, which...
We recently reported that the upregulation of adrenal G protein-coupled receptor kinase-2 (GRK2) causes enhanced catecholamine (CA) secretion by desensitizing sympatho-inhibitory alpha (2)-adrenergic receptors (alpha (2)ARs) chromaffin cells, and thereby aggravating heart failure (HF). In this study, we sought to develop an efficient reproducible in vivo gene transfer method determine whether manipulation GRK2 levels/activity regulates physiological CA rats. specifically investigated two...
Normal hearts have increased contractility in response to catecholamines. Because several lipids activate PKCs, we hypothesized that excess cellular would inhibit cardiomyocyte responsiveness adrenergic stimuli. Cardiomyocytes treated with saturated free fatty acids, ceramide, and diacylglycerol had reduced cAMP isoproterenol. This was associated PKC activation reduction of β-adrenergic receptor (β-AR) density. Pharmacological genetic inhibition prevented both palmitate-induced β-AR...
Exercise training has been reported to exert beneficial effects on cardiac function and reduce morbidity mortality of chronic heart failure (HF). Augmented sympathetic nervous system (SNS) activity, leading elevated circulating catecholamine (CA) levels, is a hallmark HF that significantly aggravates this disease. shown also SNS overactivity in HF, but the underlying molecular mechanism(s) remain unidentified. We recently adrenal G protein-coupled receptor kinase-2 (GRK2), an enzyme...
Abstract Background β 1 - and 2 –adrenergic receptors (ARs) play distinct roles in the heart, e.g. AR is pro-contractile pro-apoptotic but anti-apoptotic only weakly pro-contractile. G protein coupled receptor kinase (GRK)-2 desensitizes opposes βAR signaling by phosphorylating inducing beta-arrestin (βarr) binding. We posited herein that GRK2 blockade might enhance of subtype heart. tested effects cardiac-targeted inhibition vivo exclusively on under normal conditions heart failure (HF)....
BACKGROUND AND PURPOSE Sympathetic nervous system (SNS) hyperactivity is characteristic of chronic heart failure (HF) and significantly worsens prognosis. The success β‐adrenoceptor antagonist (β‐blockers) therapy in HF primarily attributed to protection the from noxious effects augmented catecholamine levels. β‐Blockers have been shown reduce SNS HF, but underlying molecular mechanisms are not understood. GPCR kinase‐2 (GRK2)–α 2 adrenoceptor–catecholamine production axis up‐regulated...
Heart failure (HF) remains the leading cause of morbidity and death in western world, new therapeutic modalities are urgently needed to improve lifespan quality life HF patients. The sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed mainly indicated for diabetes mellitus treatment, have been increasingly shown ameliorate heart disease, specifically HF, humans, regardless co-existence. Indeed, dapagliflozin has reported reduce cardiovascular mortality hospitalizations...
Propionic acid is a cell nutrient but also stimulus for cellular signaling. Free fatty receptor (FFAR)-3, known as GPR41, Gi/o protein-coupled (GPCR) that mediates some of the propionate's actions in cells, such inflammation, fibrosis, and increased firing/norepinephrine release from peripheral sympathetic neurons. The regulator G-protein Signaling (RGS)-4 inactivates (terminates) both Gi/o- Gq-protein signaling and, heart, protects against atrial fibrillation via calcium attenuation. RGS4...