A5016611453- Cardiac Imaging and Diagnostics
- Cardiac Valve Diseases and Treatments
- Peripheral Artery Disease Management
- Coronary Interventions and Diagnostics
- Cardiac Fibrosis and Remodeling
- Vascular Procedures and Complications
- Acute Myocardial Infarction Research
- Signaling Pathways in Disease
- Atherosclerosis and Cardiovascular Diseases
- Nitric Oxide and Endothelin Effects
- Antiplatelet Therapy and Cardiovascular Diseases
- Venous Thromboembolism Diagnosis and Management
- Cardiac, Anesthesia and Surgical Outcomes
- Cerebrovascular and Carotid Artery Diseases
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Angiogenesis and VEGF in Cancer
- Cardiac pacing and defibrillation studies
- Antioxidant Activity and Oxidative Stress
- Heart Failure Treatment and Management
- Renin-Angiotensin System Studies
- Adenosine and Purinergic Signaling
- Advanced Fluorescence Microscopy Techniques
- Cardiac and Coronary Surgery Techniques
- RNA Interference and Gene Delivery
Yale University
2013-2024
VA Connecticut Research and Education Foundation
2023
University of Ottawa
2018
Cardiovascular Research Center
2013-2014
Inserm
2012
Collège de France
2012
Centre National de la Recherche Scientifique
2012
Dartmouth–Hitchcock Medical Center
2005-2008
Dartmouth College
2007
Eli Lilly (United States)
2005
Although studies have suggested a role for angiogenesis in determining heart size during conditions demanding enhanced cardiac performance, the of EC mass normal organ is poorly understood. To explore relationship between vasculature and size, we generated transgenic mouse with regulatable expression secreted angiogenic growth factor PR39 cardiomyocytes. A significant change adult was apparent by 3 weeks following induction. Heart weight; cardiomyocyte size; vascular density normalization;...
Background— Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor −/− /ApoB-48 (HCE) mice. Methods and Results— The extent the time course of arteriogenesis after femoral artery ligation was evaluated HCE strain-matched control Distal limb perfusion measured by laser Doppler imaging, whereas MRI used visualize flow micro-computed...
Myocardial hypertrophy is an adaptation to increased hemodynamic demands. An increase in heart tissue must be matched by a corresponding expansion of the coronary vasculature maintain and adequate supply oxygen nutrients for heart. The physiological mechanisms that underlie coordination angiogenesis cardiomyocyte growth are unknown. We report induction myocardial promotes cardiac through novel NO-dependent mechanism. used transgenic, conditional overexpression placental factor (PlGF) murine...
Arteriogenesis and collateral formation are complex processes requiring integration of multiple inputs to coordinate vessel branching, growth, maturation, network size. Factors regulating these have not been determined.We used an inhibitor NFκB activation (IκBαSR) under control endothelial-specific inducible promoter selectively suppress endothelial nuclear factor-κB during development, in the adult vasculature, or vitro. Inhibition resulted excessively branched arterial that was composed...
Abstract Angiotensin receptor blocker-neprilysin inhibitor (ARNi) therapy improves the prognosis of heart failure patients. However, mechanisms remain unclear. This study investigated biological effects ARNi with neprilysin sacubitril and angiotensin blocker valsartan on myocardial remodeling cardiac perfusion in experimental (HF) after infarction (MI). Male Lewis rats (10-weeks old) confirmed HF were randomized one-week post-MI to treatment vehicle (water), sacubitril/valsartan or...
Cell migration is a dynamic process involving formation of leading edge in the direction and adhesion points from which tension generated to move cell body forward. At same time, disassembly occurs at back cell, region known as trailing edge. Syndecan-4 (S4) transmembrane proteoglycan thought be involved focal adhesions. Recent studies have shown that its cytoplasmic domain can engage signal transduction, making S4 bona fide receptor. Here, we show ligand clustering surface on endothelial...
Abstract Myocardial hypertrophy is an adaptive response to hemodynamic demands. Although angiogenesis critical support the increase in heart mass with matching blood supply, it may also promote a hypertrophic response. Previously, we showed that cardiac induced by placental growth factor (PlGF), promotes myocardial through paracrine action of endothelium-derived NO, which triggers degradation regulator G protein signaling 4 (RGS4) activate Akt/mTORC1 pathways cardiomyocytes. Here,...
Background: First-generation drug-coated balloons (DCBs) have significantly reduced the rate of restenosis compared with balloon angioplasty alone; however, high rates bailout stenting and dissections persist. The Chocolate Touch DCB is a nitinol constrained designed to reduce acute vessel trauma inhibit neointima formation restenosis. Methods: Patients claudication or ischemic rest pain (Rutherford class 2–4) superficial femoral popliteal disease (≥70% stenosis) were randomized 1:1 Lutonix...
A standard quantitative imaging approach to evaluate peripheral arterial disease does not exist. Quantitative tools for evaluating arteriogenesis in vivo are readily available, and the feasibility of monitoring serial regional changes lower extremity perfusion has been examined.Serial muscle were evaluated after femoral artery occlusion a porcine model using single photon emission tomography (SPECT)/CT with postmortem validation findings gamma counting, imaging, histological analysis. Hybrid...
Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography found have no obstructive artery disease (CAD). Ischemia and nonobstructive arteries (INOCA) is increasingly recognized encompasses microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, other vasomotor disorders. However, the prevalence these disorders whether underlying atherosclerotic plaque burden morphology affect long-term outcomes each physiologic phenotype unknown.
Angiogenic therapy with individual growth factors or "master switch" genes is being evaluated for treatment of advanced coronary artery disease. In this study, we investigated the efficacy and mechanism PR39, a gene capable activating VEGF fibroblast factor (FGF)-2-dependent pathways. PR39 enhances hypoxia-inducible factor-1alpha (HIF-1alpha)-dependent expression by selectively inhibiting proteasome degradation transcription factor. addition, also stimulates FGF receptors (FGFR)-1...
PR-39, a proline-arginine-rich angiogenic response peptide, has been implicated in myocardial ischemic reperfusion injury. The present study examined the cardioprotective abilities of PR39 gene therapy. Male C57Bl/J6 mice were randomized to intramyocardial injecton 10(9) p.f.u. adenovirus encoding (PR39), FGFR1 dominant negative signaling construct (FGFR1-dn), empty vector (EV), or plus 4 microg plasmid endcoding HIF1alpha (PR39 + HIF1alpha-dn). Seven days later, hearts subjected 20 min...