A5003632963- Nitric Oxide and Endothelin Effects
- Renin-Angiotensin System Studies
- Protein Kinase Regulation and GTPase Signaling
- Signaling Pathways in Disease
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
- Angiogenesis and VEGF in Cancer
- Ion Transport and Channel Regulation
- Coronary Interventions and Diagnostics
- Adipose Tissue and Metabolism
- Melanoma and MAPK Pathways
- Hormonal Regulation and Hypertension
- Protease and Inhibitor Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Cardiovascular Health and Disease Prevention
- Apelin-related biomedical research
- Cancer, Hypoxia, and Metabolism
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Antioxidant Activity and Oxidative Stress
University of Rochester
2016-2025
University of Rochester Medical Center
2009-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2013
University of Wyoming
2013
Centro Cardiologico Monzino
2013
Shanghai Jiao Tong University
2012
Cardiovascular Research Foundation
2011
Tohoku University
2011
Cardiovascular Institute Hospital
2007-2010
University of Pittsburgh at Bradford
2009
Abstract —Mechanical forces are important modulators of cellular function in many tissues and particularly the cardiovascular system. The endothelium, by virtue its unique location vessel wall, responds rapidly sensitively to mechanical conditions created blood flow cardiac cycle. In this study, we examine data which suggest that steady laminar shear stress stimulates responses essential for endothelial cell atheroprotective. We explore ability modulate atherogenesis via effects on...
Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, addition platelet-derived growth factors, factors from inflammatory and endothelial at the site of injury may contribute VSMC proliferation. We hypothesized that a common mechanism by which stimulate could be active oxygen species (i.e., O2-, H2O2, .OH) generated during Using xanthine/xanthine oxidase generate species, we studied effects these agents on growth. Xanthine/xanthine...
To investigate the role of vasoconstrictor hormones in vascular smooth muscle cell growth we have studied effects potent angiotensin II on a cultured rat aortic model. Angiotensin was not mitogenic for these cells, as assessed by determining number, nor it synergistic this regard with 10% calf serum. However, 24-hour exposure to 100 nM caused an 80% increase protein synthesis (compared 0.4% serum control) measured tritiated leucine incorporation. This "hypertrophic" response indicated 30%...
Endothelial cells release nitric oxide (NO) more potently in response to increased shear stress than agonists which elevate intracellular free calcium concentration ([Ca 2+ ] i ). To determine mechanistic differences the regulation of endothelial constitutive NO synthase (ecNOS), we measured production by bovine aortic exposed a laminar flow chamber or treated with Ca ionophores static culture. The kinetics cumulative varied strikingly: (25 dyne/cm 2 ) stimulated biphasic increase over...
Mitogen-activated protein (MAP) kinases are a multigene family activated by many extracellular stimuli. There three groups of MAP based on their dual phosphorylation motifs, TEY, TPY, and TGY, which termed signal-regulated (ERK1/2), c-Jun N-terminal kinases, p38, respectively. A new kinase member Big 1 (BMK1) or ERK5 was recently cloned. BMK1 has TEY sequence similar to ERK1/2 but unique COOH-terminal loop-12 domains. To define regulation, its activation in cultured rat vascular smooth...
Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells that has been implicated in the pathogenesis of atherosclerosis. The potential role PDGF altered vasoreactivity atherosclerotic vessels studied through an examination its effects on contractility rat aorta. caused concentration-dependent contraction aortic strips and was significantly more molar basis than classic vasoconstrictor peptide angiotensin II. Furthermore, increased cytosolic free calcium...
Abstract Increased generation of active oxygen species such as H 2 O and − may be important in vascular smooth muscle cell growth associated with atherosclerosis restenosis. In previous work, we showed that stimulated proto-oncogene expression. the present study, compared effects on cultured rat aortic signal transduction. was generated a concentration-dependent manner by naphthoquinolinedione LY83583. Vascular growth, measured [ 3 H]thymidine incorporation, 200 μmol/L (110% increase versus...
Vasoconstrictors such as angiotensin I1 (Ang 11) play an important role in the pathogenesis of hypertension.These agonists may be responsible for abnormal vascular smooth muscle cell (VSMC) growth seen hypertension, either indirectly a consequence elevating blood pressure or directly result receptor-mediated effects on VSMC growth.To investigate whether Ang might initiate modulate some "early" genetic programs associated with VSMC, expression proto-oncogene c-fos was studied cultured rat...
Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced endothelial NO synthase (eNOS) plays an essential role in regulation function structure flow, but molecular mechanisms that transduce mechanical force to eNOS activation are not well understood. In this study, we found laminar flow (shear stress=12 dyne/cm 2 ) rapidly activates growth factor receptor (VEGFR2)...
Recent data suggest that uric acid is generated locally in the vessel wall by action of xanthine oxidase. This enzyme, activated during ischemia/reperfusion proteolytic conversion dehydrogenase, catalyzes oxidation xanthine, thereby generating free radicals and acid. Because potential role vascular disease, we studied effects on rat aortic smooth muscle cell (VSMC) growth. Uric stimulated VSMC DNA synthesis, as measured [3H]thymidine incorporation, a concentration-dependent manner with...
Abstract —Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis, hypertension, and restenosis, part by promoting vascular smooth muscle cell (VSMC) growth. Many VSMC growth factors are secreted act an autocrine manner. Here we demonstrate that cyclophilin A (CyPA), a member immunophilin family, is VSMCs response to oxidative stress mediates extracellular signal–regulated kinase (ERK1/2) activation reactive species. Human recombinant CyPA can mimic effects...
Endothelial cells release nitric oxide (NO) acutely in response to increased laminar fluid shear stress, and the increase is correlated with enhanced phosphorylation of endothelial nitric-oxide synthase (eNOS). Phosphoamino acid analysis eNOS from bovine aortic labeled [32P]orthophosphate demonstrated that only phosphoserine was present under both static flow conditions. Fluid stress induced phosphate incorporation into two specific tryptic peptides as early 30 s after initiation flow. The...
Abstract Local alterations in the hemodynamic environment regulate endothelial cell function, but signal-transduction mechanisms involved this process remain unclear. Because mitogen-activated protein (MAP) kinases have been shown to be activated by physical forces, we measured phosphorylation and enzyme activity of MAP kinase identify signal events response fluid shear stress. Flow at physiological stress (3.5 117 dynes/cm 2 ) 42-kD 44-kD present cultured bovine aortic cells, with maximal...
Big mitogen-activated kinase 1 (BMK1) or extracellular signal-regulated kinase-5 (ERK5) has recently been identified as a new member of the protein family. We have shown that BMK1 is activated to greater extent by H<sub>2</sub>O<sub>2</sub> than growth factors, suggesting in comparison with other family members, redox-sensitive kinase. Previous investigations indicate tyrosine c-Src mediates signal transduction reactive oxygen species, including H<sub>2</sub>O<sub>2</sub>. Therefore, role...