A5046113390- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pulmonary Hypertension Research and Treatments
- Renin-Angiotensin System Studies
- Eicosanoids and Hypertension Pharmacology
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac Ischemia and Reperfusion
- Atherosclerosis and Cardiovascular Diseases
- Phagocytosis and Immune Regulation
- Cardiovascular Health and Disease Prevention
- Angiogenesis and VEGF in Cancer
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Redox biology and oxidative stress
- Advanced Glycation End Products research
- Adenosine and Purinergic Signaling
- Hormonal Regulation and Hypertension
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Disease and Adiposity
- Apelin-related biomedical research
- Cancer-related molecular mechanisms research
- Vitamin C and Antioxidants Research
- S100 Proteins and Annexins
- DNA Repair Mechanisms
- Cardiovascular Function and Risk Factors
University of Pittsburgh
2016-2025
University of Connecticut
2023
Reproductive Medicine Institute
2012-2019
Division of Chemistry
2019
University of Bío-Bío
2014
Henry Ford Hospital
2001-2010
Jewish General Hospital
2010
McGill University
2010
Medizinische Hochschule Hannover
2010
Henry Ford Health System
2003-2008
Oxidative stress has been implicated in the pathophysiology of myocardial failure. We tested hypothesis that oxidative can regulate extracellular matrix cardiac fibroblasts. Neonatal and adult rat fibroblasts vitro were exposed to H 2 O (0.05–5 μM) or superoxide-generating system xanthine (500 plus oxidase (0.001–0.1 mU/ml) (XXO) for 24 h. In-gel zymography demonstrated XXO each increased gelatinase activity corresponding metalloproteinases (MMP) MMP-13, MMP-2, MMP-9. decreased collagen...
We previously reported enhanced expression of the p67 phox and gp91 components NAD(P)H oxidase in angiotensin (Ang) II–induced hypertension, suggesting de novo assembly response to Ang II. To examine direct involvement oxidases O 2 − production, we designed a chimeric peptide that inhibits p47 association with (gp91ds- tat ). This was achieved by linking 9-amino acid (aa) derived from HIV-coat protein ( ) 9-aa sequence (known interact As control, constructed chimera containing scrambled...
A major source of vascular smooth muscle cell (VSMC) superoxide is NAD(P)H oxidase. However, the molecular characteristics and regulation this enzyme are unclear. We investigated whether VSMCs from human resistance arteries (HVSMCs) possess a functionally active, angiotensin II (Ang II)-regulated oxidase that contains neutrophil subunits, including p22phox, gp91phox, p40phox, p47phox, p67phox. mRNA expression gp91phox homologues, nox1 nox4, was also assessed in HVSMCs, aortic cells, rat...
Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating cell proliferation and migration, primarily through the receptor tyrosine kinase VEGF receptor2 (Flk1/KDR). Reactive oxygen species (ROS) derived from NAD(P)H oxidase are critically important in many aspects of vascular regulation, both small GTPase Rac1 gp91 phox critical components complex. A role VEGF-induced angiogenesis, however, has not been defined. In present study, electron spin resonance spectroscopy is...
Superoxide anion (O 2 − ) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated development hypertension. In previous studies, we found that O is produced predominantly adventitia isolated rabbit aorta acts as barrier to NO. present characterize enzyme responsible for production show this constitutively active NADPH oxidase with similar composition phagocyte oxidase. Constitutive -generating activity was localized aortic...
The purpose of this study was to determine whether superoxide anion is produced endogenously in the rat aortic adventitia and sufficient interfere with response aorta nitric oxide. Relaxation measured rings thoracic aorta, which were oriented so that adventitial or luminal surface could be preferentially exposed oxide sodium nitroprusside. To accomplish this, mounted (1) facing outward, (2) inward after inverting, (3) outward inverting twice (to control for procedure). relaxation oxide, but...
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation determined that a critical...
Oxidative stress stimulates both growth and apoptosis in cardiac myocytes vitro. We investigated whether oxidative mediates hypertrophy cyclically stretched ventricular myocytes. Neonatal rat cultured on laminin-coated silastic membranes were (1 Hz) at low (nominal 5%) high 25%) amplitudes for 24 hours. Stretch caused a graded increase superoxide anion production as assessed by dismutase (SOD)-inhibitable cytochrome c reduction or electron paramagnetic resonance spectroscopy. The role of...
Angiotensin II-induced hypertension is associated with NAD(P)H oxidase-dependent superoxide production in the vessel wall. Vascular level also increased deoxycorticosterone acetate (DOCA)-salt hypertension, which a markedly depressed plasma renin activity because of sodium retention. However, mechanisms underlying low-renin are undefined.This study investigated (1) whether and how endothelin-1 (ET-1), DOCA-salt hypertensive rats, contributes to arterial generation (2) effect gene transfer...
Superoxide anion can modulate vascular smooth muscle tone and potentially affect the growth response in disease. The present studies were undertaken to characterize source of superoxide rabbit aorta. Rings aorta (5 mm) incubated physiological salt solution (PSS) for 30 min at 37 degrees C presence 10 mM diethyldithiocarbamate (DDC) with or without inhibitors superoxide-generating systems. then placed PSS containing 250 microM lucigenin absence inhibitors, changes amounts determined by...
Abstract —Oxidative stress has been implicated in the pathophysiology of myocardial failure. We tested hypothesis that inhibition endogenous antioxidant enzymes can regulate phenotype cardiac myocytes. Neonatal rat ventricular myocytes vitro were exposed to diethyldithiocarbamic acid (DDC), an inhibitor cytosolic (Cu, Zn) and extracellular superoxide dismutase (SOD). DDC inhibited SOD activity increased intracellular a concentration-dependent manner. A low concentration (1 μmol/L) stimulated...
Abstract —Superoxide radical (O 2 − ) is ubiquitously critical to the bioactivity of endothelial nitric oxide. In angiotensin-dependent hypertension, vascular O levels rise and impede endothelium/nitric oxide–dependent relaxation. We have reported that major source in rabbit aorta adventitial fibroblast phagocyte-like NADPH oxidase shown angiotensin (Ang) II treatment fibroblasts causes a concentration-dependent increase particulate NADPH-dependent . From cultured aortic treated or not with...
Nonenzymatic glycation that results in the production of early-glycation Amadori-modified proteins and advanced-glycation end products may be important pathogenesis diabetic complications. However, effects early-glycated proteins, such as glycated serum albumin (Gly-BSA), are poorly defined. In this study, we investigated Gly-BSA on reactive oxygen species (ROS) by cardiomyocytes.Cultured neonatal rat cardiomyocytes were incubated with or vehicle (bovine [BSA]) for up to 48 hours....
Angiotensin II (Ang II)-induced hypertension is associated with an inflammatory response that may contribute to the development of target organ damage. We tested hypothesis that, in Ang II-induced hypertension, CC chemokine receptor 2 (CCR2) activation plays important role renal fibrosis, damage, and dysfunction by causing oxidative stress, macrophage infiltration, cell proliferation. To test this hypothesis, we used CCR2 knockout mice (CCR2-/-). The natural ligand monocyte chemoattractant...
AimsThrombospondin-1 (TSP1), via its necessary receptor CD47, inhibits nitric oxide (NO)-stimulated soluble guanylate cyclase activation in vascular smooth muscle cells, and TSP1-null mice have increased shear-dependent blood flow compared with wild-type mice. Yet, the endothelial basement membrane should theory function as a barrier to diffusion of TSP1 into arterial cell layer. These findings suggested that endothelial-dependent differences may be result direct modulation NO synthase...
Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach determine if spontaneous nuclear DNA damage sufficient initiate mammals. Ercc1-/∆ mice with reduced expression ERCC1-XPF endonuclease have impaired capacity repair the genome. accumulated spontaneous, oxidative more rapidly than wild-type (WT) mice. As consequence, compared repair-competent animals. levels never...
Abstract Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial (mtDNA) that are predicted to form G4 enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports ability mtDNA cancer cells; however, functional roles regulating mitochondrial nucleic acid homeostasis non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging...
Objective— Our preliminary data suggested that angiotensin II (Ang II)–induced reactive oxygen species are involved in intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration the rat thoracic aorta. Other reports demonstrating species–induced cell growth a potential role of NAD(P)H oxidase vascular hypertrophy. In present study, we postulate is functionally Ang II–induced ICAM-1 expression, macrophage infiltration, growth, inhibition attenuates these processes...