A5028352991- Extracellular vesicles in disease
- Cardiovascular Disease and Adiposity
- Nitric Oxide and Endothelin Effects
- Diabetes Treatment and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiovascular Function and Risk Factors
- Calpain Protease Function and Regulation
- Tissue Engineering and Regenerative Medicine
- FOXO transcription factor regulation
- Cardiac Ischemia and Reperfusion
- Circular RNAs in diseases
- Pancreatic function and diabetes
- Angiogenesis and VEGF in Cancer
- Cardiac Fibrosis and Remodeling
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
- Cancer-related gene regulation
- Electrospun Nanofibers in Biomedical Applications
- Cardiovascular Effects of Exercise
- Atherosclerosis and Cardiovascular Diseases
- Metabolism, Diabetes, and Cancer
- Apelin-related biomedical research
- Adipose Tissue and Metabolism
Rhode Island Hospital
2016-2025
Brown University
2016-2025
National Institutes of Health
2025
National Institute of Allergy and Infectious Diseases
2025
Providence College
2015-2024
Karachi Medical and Dental College
2024
Rhode Island Foundation
2024
National Heart Lung and Blood Institute
2024
John Brown University
2021-2024
Cardiovascular Research Center
2015-2022
Regulation of vascular endothelial (VE) growth factor (VEGF)–induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation VEGF receptor 2 (VEGFR2) at Y951 facilitates binding VEGFR2 to the Rous sarcoma (Src) homology 2-domain T cell–specific adaptor (TSAd), which turn regulates VEGF-induced activation c-Src kinase permeability. was activated vivo vitro a VEGF/TSAd-dependent manner, regulated via increased pY418 reduced pY527. Tsad...
FLICE-inhibitory protein (FLIP) is a homolog of caspase-8 that lacks catalytic activity and has been shown to be important in protecting endothelial cells from apoptosis. The serine/threonine kinase Akt/PKB was recently reported promote FLIP expression tumor cells. Here we examined the role forkhead transcription factor FOXO3a, downstream target Akt, controlling regulation FOXO3a nuclear translocation regulated by Akt human umbilical vein Transduction nonphosphorylatable, constitutively...
Objective— Vascular endothelial growth factor (VEGF) is a potent angiogenic that promotes cell (EC) survival, migration, and permeability. The forkhead transcription factors FKHR, FKHRL1, AFX are mammalian orthologues of DAF-16, protein controls longevity in Caenorhabditis elegans . In this study, we examined whether VEGF coupled to phosphatidyl inositol 3-kinase (PI3K)/Akt/forkhead ECs. Methods Results— We demonstrate human ECs express members the family (FKHR, AFX) modulates...
Activation and dysfunction of the endothelium underlie many vascular disorders including atherosclerosis, tumor growth, inflammation. Endothelial cell activation is mediated by different extra-cellular signals, which result in overlapping yet distinct patterns gene expression. Here we show, DNA microarray analyses, that endothelial growth factor (VEGF) thrombin dramatic rapid upregulation Down syndrome critical region (DSCR)-1 encoding exons 4-7, a negative feedback regulator...
Vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) play critical roles in vascular physiology pathophysiology. We have demonstrated previously that NADPH oxidase-derived ROS are required for VEGF-mediated migration proliferation of cells. The goal this study was to determine the extent which VEGF signaling is coupled oxidase activity. Human umbilical vein cells and/or human coronary artery were transfected with short interfering RNA against p47(phox) subunit oxidase,...
Background Sodium-glucose cotransporter-2 inhibitors are cardioprotective independent of glucose control, as demonstrated in animal models acute myocardial ischemia and clinical trials. The functional molecular mechanisms these benefits the setting chronic poorly defined. purpose this study is to determine effects canagliflozin therapy on perfusion, fibrosis, function a large model ischemia. Methods Results Yorkshire swine underwent placement an ameroid constrictor left circumflex artery...
NADPH oxidase has been shown to play an important role in cardiovascular biology. The goal of the present study was determine whether activity is for endothelial cell growth and migration. In proliferation assays, factor- or serum-induced DNA synthesis three different types human cells abrogated by inhibitors oxidase, but not xanthine nitric oxide synthase. Moreover, vascular factor-induced migration suppressed presence inhibitors. These results support a potential mediating angiogenesis.
Vascular endothelial growth factor (VEGF) is a potent vascular cell-specific mitogen that modulates cell function. In the present study, we show VEGF induces manganese-superoxide dismutase (MnSOD) mRNA and protein in human coronary artery cells (HCAEC) pulmonary cells. VEGF-mediated induction of MnSOD was inhibited by pretreatment with NADPH oxidase inhibitors, diphenyleneiodonium (DPI), 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not nitric oxide synthase inhibitor L-NAME...
Vascular smooth muscle cell (VSMC) proliferation and migration contribute significantly to atherosclerosis, postangioplasty restenosis, transplant vasculopathy. Forkhead transcription factors belonging the FoxO subfamily have been shown inhibit growth cycle progression in a variety of types. We hypothesized that forkhead proteins may play role VSMC biology. Under vitro conditions, platelet-derived factor (PDGF)-BB, tumor necrosis factor-α, insulin-like 1 stimulated phosphorylation human...
Rationale : Forkhead box-O transcription factors (FOXOs) transduce a wide range of extracellular signals, resulting in changes cell survival, cycle progression, and several type-specific responses. FOXO1 is expressed many types, including endothelial cells (ECs). Previous studies have shown that Foxo1 knockout mice results embryonic lethality at E11 because impaired vascular development. In contrast, somatic deletion associated with hyperproliferation ECs. Thus, the precise role endothelium...
Age-associated decline in cardiovascular function is believed to occur from the deleterious effects of reactive oxygen species (ROS). However, failure recent clinical trials using antioxidants patients with disease, and findings showing paradoxical role for NADPH oxidase-derived ROS endothelial challenge this long-held notion against ROS. Here, we examine endothelium-specific conditional increase on coronary function. We have generated a novel binary (Tet-ON/OFF) transgenic mouse...
Mesenchymal stem cell-derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was examine the effects human mesenchymal EV injection on cardiac function, blood flow, and vessel density setting chronic ischemia. Twenty-three Yorkshire swine underwent placement an ameroid constrictor their left circumflex artery. Two weeks later, animals were split into 2 groups: control group (CON; n=7) (MVM; n=10). MVM 50 μg EVs mL 0.9%...
We recently demonstrated that thrombin induces the expression of vascular adhesion molecule-1 (VCAM-1) in endothelial cells by an NF-κB- and GATA-dependent mechanism. In present study, we describe signaling pathways mediate this response. Thrombin stimulation VCAM-1 gene promoter human umbilical vein was inhibited preincubation with phosphatidylinositol 3-kinase inhibitor, LY294002, protein kinase C (PKC)-δ rottlerin, a PKC-ζ peptide or overexpression dominant negative (DN)-PKC-ζ....
There are conflicting reports on the role of reactive oxygen species (ROS) i.e. beneficial vs. harmful, in vascular endothelium. Here, we aim to examine whether duration exposure ROS and/or subcellular levels responsible for apparently paradoxical effects oxidants We have recently generated binary (Tet-ON/OFF) conditional transgenic mice (Tet-Nox2:VE-Cad-tTA) that can induce 1.8 ± 0.42-fold increase NADPH oxidase (NOX)-derived specifically endothelium upon withdrawal tetracycline from...
ObjectiveLimited treatments exist for nonoperative chronic coronary artery disease. Previously, our laboratory has investigated extracellular vesicle (EV) therapy as a potential treatment disease using swine model and demonstrated improved cardiac function in treated with intramyocardial EV injection. Here, we seek to investigate the benefits of EVs by hypoxia-conditioned (HEV). Specifically, this study aims effect HEV on apoptosis chronically ischemic myocardium swine.MethodsFourteen...