A5060967318- Adipokines, Inflammation, and Metabolic Diseases
- Angiogenesis and VEGF in Cancer
- Adipose Tissue and Metabolism
- Cardiovascular Disease and Adiposity
- Acute Myeloid Leukemia Research
- Muscle Physiology and Disorders
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Congenital heart defects research
- Cardiac Fibrosis and Remodeling
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Nitric Oxide and Endothelin Effects
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- RNA Research and Splicing
- FOXO transcription factor regulation
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Signaling Pathways in Disease
- Coronary Interventions and Diagnostics
University of Virginia
2018-2025
Virginia Tech
2024
University of North Carolina at Chapel Hill
2021-2024
Carilion Clinic
2024
Walsh University
2011-2023
Kansai Medical University
2023
Boston University
2012-2022
Kidderminster Hospital and Treatment Centre
2022
Morristown Medical Center
1993-2021
University Surgical Associates
2021
Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several these recurrent mutations, including those the gene encoding epigenetic modifier enzyme TET2, promote expansion mutant blood This clonal hematopoiesis correlates risk atherosclerotic cardiovascular disease. We studied effects Tet2-mutant cells atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. found that partial bone marrow reconstitution TET2-deficient...
Background —Preclinical studies have indicated that angiogenic growth factors can stimulate the development of collateral arteries, a concept called “therapeutic angiogenesis.” The objectives this phase 1 clinical trial were (1) to document safety and feasibility intramuscular gene transfer by use naked plasmid DNA encoding an endothelial cell mitogen (2) analyze potential therapeutic benefits in patients with critical limb ischemia. Methods Results —Gene was performed 10 limbs 9 nonhealing...
Although increased external load initially induces cardiac hypertrophy with preserved contractility, sustained overload eventually leads to heart failure through poorly understood mechanisms. Here we describe a conditional transgenic system in mice characterized by the sequential development of adaptive contractility acute phase and dilated cardiomyopathy chronic following induction an activated Akt1 gene heart. Coronary angiogenesis was enhanced during growth but reduced as hearts underwent...
Background —IGF-1 has been shown to protect myocardium against death in animal models of infarct and ischemia-reperfusion injury. In the present study, we investigated role IGF-1–regulated protein kinase Akt cardiac myocyte survival vitro vivo. Methods Results promoted cultured cardiomyocytes under conditions serum deprivation a dose-dependent manner but had no effect on fibroblast survival. The cytoprotective IGF-1 was abrogated by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor...
Resveratrol may protect against metabolic disease through activating SIRT1 deacetylase. Because we have recently defined AMPK activation as a key mechanism for the beneficial effects of polyphenols on hepatic lipid accumulation, hyperlipidemia, and atherosclerosis in type 1 diabetic mice, hypothesize that polyphenol-activated acts upstream signaling hepatocellular metabolism. Here show polyphenols, including resveratrol synthetic polyphenol S17834, increase deacetylase activity, LKB1...
Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro vivo. stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures functioned as a chemoattractant migration assays. promoted phosphorylation AMP-activated protein kinase (AMPK), Akt/protein B, endothelial nitric oxide synthesis (eNOS) HUVECs. Transduction...
Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These EPCs are derived bone marrow mobilized endogenously response tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay vitro EPC culture simvastatin-treated animals vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments population EPCs....
Adiponectin is an adipocyte-derived, antiatherogenic protein that present in serum as three isoforms. Total adiponectin levels are decreased obese or diabetic humans animal models. This study was designed to elucidate the relative isoform distribution of human disease states and identify active form toward vascular endothelial cells. The percentage high molecular weight (HMW) per total significantly lower patients with coronary artery than control subjects, whereas hexamer similar trimer...
During terminal differentiation of skeletal myoblasts, cells fuse to form postmitotic multinucleated myotubes that cannot reinitiate DNA synthesis. Here we investigated the temporal relationships among these events during in vitro C2C12 myoblasts. Cells expressing myogenin, a marker for entry myoblasts into pathway, were detected first myogenesis, followed by appearance mononucleated both myogenin and cell cycle inhibitor p21. Although expression proteins was sustained mitogen-restimulated...
Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These EPCs are derived bone marrow mobilized endogenously response tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay vitro EPC culture simvastatin-treated animals vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments population EPCs....
Angiotensin II, a hypertrophic/anti-apoptotic hormone, utilizes reactive oxygen species (ROS) as growth-related signaling molecules in vascular smooth muscle cells (VSMCs). Recently, the cell survival protein kinase Akt/protein B (PKB) was proposed to be involved synthesis. Here we show that angiotensin II causes rapid phosphorylation of Akt/PKB (6- ± 0.4-fold increase). Exogenous H2O2 (50–200 μm) also stimulates (maximal 8- 0.2-fold increase), suggesting activation is redox-sensitive. Both...
Regulation of endothelial cell apoptosis is a critical modulator normal and pathological angiogenesis. In this study, we examined the role protein kinase Akt/PKB in survival response to growth factor matrix attachment signals. Vascular factor(VEGF)-induced cytoprotection monolayers correlated with wortmannin-sensitive induction Akt activity. Transfection an adenovirus expressing dominant-negative mutant decreased viability presence VEGF. Conversely, adenoviral transduction wild-type...