A5000841232- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Protein Kinase Regulation and GTPase Signaling
- Redox biology and oxidative stress
- Eicosanoids and Hypertension Pharmacology
- S100 Proteins and Annexins
- Cellular Mechanics and Interactions
- Hormonal Regulation and Hypertension
- Immune Response and Inflammation
- Barrier Structure and Function Studies
- Atherosclerosis and Cardiovascular Diseases
- Mitochondrial Function and Pathology
- Protease and Inhibitor Mechanisms
- RNA Research and Splicing
- Ion channel regulation and function
- Bone Metabolism and Diseases
- Connective tissue disorders research
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Angiogenesis and VEGF in Cancer
- Bone and Dental Protein Studies
- Caveolin-1 and cellular processes
Emory University
2015-2025
Georgia Institute of Technology
2004-2015
The Wallace H. Coulter Department of Biomedical Engineering
2004-2014
Atlanta VA Medical Center
2014
University of North Carolina at Chapel Hill
2012
Howard Hughes Medical Institute
2012
UNC Lineberger Comprehensive Cancer Center
2012
Kindai University
2009
University of Geneva
2009
National University
2009
NAD(P)H oxidases are important sources of superoxide in the vasculature, activity which is associated with risk factors for human atherosclerosis. This study was designed to investigate localization production and expression Nox family oxidase proteins (gp91phox, Nox1, Nox4) nonatherosclerotic atherosclerotic coronary arteries.In artery segments from explanted hearts, we examined intracellular dihydroethidium. In arteries, present homogenously throughout intima, media, adventitia. there an...
Abstract —Emerging evidence indicates that reactive oxygen species are important regulators of vascular function. Although NAD(P)H oxidases have been implicated as major sources superoxide in the vessel wall, molecular identity these proteins remains unclear. We recently cloned nox1 (formerly mox-1), a member new family gp91 phox homologues, and showed it is expressed proliferating smooth muscle cells (VSMCs). In this study, we examined expression three nox members, nox1, nox4, , VSMCs,...
Angiotensin II infusion causes endothelial dysfunction by increasing NAD(P)H oxidase-mediated vascular superoxide production. However, it remains to be elucidated how in vivo angiotensin treatment may alter the expression of gp91 phox isoforms and nitric oxide synthase (NOS III) subsequent signaling events whether, addition oxidase, NOS III contributes formation. We therefore studied influence (7 days) rats on function oxidase subunits p22 , nox1, nox4, III. Further analysis included...
Restenosis, a frequent complication of coronary angioplasty, is associated with increased superoxide (O 2 · − ) production. Although the molecular identity responsible oxidase unclear, an NAD(P)H appears to be involved. In smooth muscle, p22phox and homologues gp91phox, nox1 nox4, are expressed, whereas fibroblasts contain gp91phox. To begin investigating possibility that these components might contribute O accompanies neointimal formation, we measured their expression after balloon injury...
Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources reactive vessel wall, but importance individual Nox homologues specific layers vascular wall is unclear. Nox1 upregulation has pathologies such as hypertension and restenosis.To investigate pathological role smooth muscle, transgenic mice overexpressing muscle cells (TgSMCnox1) were created, impact on medial hypertrophic response during angiotensin...
Rationale: NADPH oxidases (Noxes) regulate vascular physiology and contribute to the pathogenesis of disease. In smooth muscle cells (VSMCs), interactions individual Nox homologs with regulatory proteins are poorly defined. Objective: The objective this study was identify novel oxidase proteins. Methods Results: Using a yeast 2-hybrid screen, we identified p22phox binding partner, Poldip2, demonstrated that it associates p22phox, (Nox)1, Nox4 colocalizes at sites localization. Poldip2...
Angiotensin II is a multifunctional hormone that affects both contraction and growth of vascular smooth muscle cells through complex series intracellular signaling events initiated by the interaction angiotensin with AT 1 receptor. The cellular response to multiphasic, involving stimulation within seconds phospholipase C Ca 2+ mobilization; activation minutes D, A 2 , protein kinase C, MAP kinase; after period hours gene transcription NADH/NADPH oxidase activity. also activates numerous...
Atherosclerosis is an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions including oscillatory shear stress (OS). OS exposure induces endothelial expression of bone morphogenic protein 4 (BMP4), which turn may activate intercellular adhesion molecule-1 (ICAM-1) and monocyte adhesion. also known induce by producing reactive oxygen species (ROS) from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, raising the possibility...
Objective— The mechanisms responsible for maintaining the differentiated phenotype of adult vascular smooth muscle cells (VSMCs) are incompletely understood. Reactive oxygen species (ROS) have been implicated in VSMC differentiation, but sources unknown. In this study, we investigated role Nox1 and Nox4-derived ROS process. Methods Results— Primary VSMCs were used to study relationship between Nox homologues differentiation markers such as α-actin (SM α-actin), myosin heavy chain (SM-MHC),...
Angiotensin II (AngII)-induced superoxide (O2(•-)) production by the NADPH oxidases and mitochondria has been implicated in pathogenesis of endothelial dysfunction hypertension. In this work, we investigated specific molecular mechanisms responsible for stimulation mitochondrial O2(•-) its downstream targets using cultured human aortic cells a mouse model AngII-induced hypertension.Western blot analysis showed that Nox2 Nox4 were present cytoplasm but not mitochondria. Depletion Nox2, Nox1,...
Shear stress regulates endothelial nitric oxide and superoxide (O 2 −· ) production, implicating the role of NADPH oxidase activity. It is unknown whether shear sources reactive species consequent low-density lipoprotein (LDL) modification, initiation inflammatory events. Bovine aortic cells (BAECs) in presence 50 μg/mL native LDL were exposed to (1) pulsatile flow with a mean (τ ave 25 dyne/cm (2) oscillating at τ 0. After 4 hours, aliquots culture medium collected for high-performance...
Recently, we demonstrated that the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, either 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ ) or ciglitazone, increased endothelial nitric oxide (·NO) release without altering synthase (eNOS) expression ( 4 ). However, precise molecular mechanisms of PPAR-γ-stimulated endothelial·NO remain to be defined. Superoxide anion radical (O − ·) combines with ·NO decrease·NO bioavailability. NADPH oxidase, which produces O ·, and...
Vascular NADPH oxidases (Noxes) have been implicated in cardiovascular diseases; however, the importance of individual Nox homologues remains unclear. Here, role vascular smooth muscle cell (VSMC) Nox1 neointima formation was studied using genetically modified animal models.Wire injury-induced femoral artery, along with proliferation and apoptosis, reduced Nox1(y/-) mice, but there little difference Tg(SMCnox1) mice compared wild-type (WT) mice. Proliferation migration were cultured VSMCs...
Abstract —Caveolae are membrane domains that have been implicated in signal transduction, and caveolins major structural components of these domains. We found all reported caveolin isoforms (caveolin-1, -2, -3) were expressed vascular smooth muscle cells (VSMCs); however, only caveolin-1 mRNA was regulated by angiotensin II (Ang II). Ang (100 nmol/L) increased mRNA, with a peak at 2 hours (193±6% control, P <0.01, n=4). In contrast, significantly decreased protein, nadir 4 (64±5% n=6). [...
Abstract Background Sepsis-associated encephalopathy (SAE), a diffuse cerebral dysfunction in the absence of direct CNS infection, is associated with increased rates mortality and morbidity patients sepsis. Increased cytokine production disruption blood-brain barrier (BBB) are implicated pathogenesis SAE. The induction pro-inflammatory mediators driven, part, by activation NF-κΒ. Lipopolysaccharide (LPS), an endotoxin produced gram-negative bacteria, potently activates NF-κΒ its downstream...
The vascular angiotensin II (ANG II) receptor (AT1) is a central component of the renin-angiotensin system; thus, regulation its expression likely to be important in cardiovascular responsiveness. We demonstrate that ANG down-regulates rat aortic smooth muscle cells. Incubation for 4 hr with 100 nM decreased AT1 mRNA and protein by 70% 35%, respectively. This homologous down-regulation was concentration time dependent blocked antagonist losartan. It did not appear mediated kinase C or other...
Restenosis after percutaneous transluminal coronary angioplasty is the major limitation of long-term success this procedure. The process restenosis similar to an accelerated form atherosclerosis. Thus, therapeutic interventions that limit progression and initiation atherosclerosis may be beneficial in treatment restenosis. One such intervention antioxidant drug probucol, which has demonstrated benefit animal models atherosclerosis.Twenty-six female domestic swine were divided into three...