A5069070315- Nitric Oxide and Endothelin Effects
- Adipose Tissue and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Muscle Physiology and Disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Eicosanoids and Hypertension Pharmacology
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Circadian rhythm and melatonin
- Heart Rate Variability and Autonomic Control
- Renin-Angiotensin System Studies
- Cardiovascular Health and Disease Prevention
- Diet, Metabolism, and Disease
- Cardiovascular Disease and Adiposity
- Regulation of Appetite and Obesity
- Hormonal Regulation and Hypertension
- Diet and metabolism studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Muscle metabolism and nutrition
- Cancer, Hypoxia, and Metabolism
- Pulmonary Hypertension Research and Treatments
- Cardiac electrophysiology and arrhythmias
- Cardiac Imaging and Diagnostics
- Antioxidant Activity and Oxidative Stress
Augusta University
2016-2025
Center for Vascular Biology Research
2007-2025
Augusta University Health
2011-2023
Sanofi (United States)
2023
Charlie Norwood VA Medical Center
2018
Jesse Brown VA Medical Center
2018
University of Arizona
2018
University of Illinois Chicago
2018
Georgia Regents Medical Center
2013-2016
University of Kentucky
2016
Cardiovascular disease is the leading cause of death for both men and women in United States world. A profound pattern exists time day at which occurs; it morning, when endothelium most vulnerable blood pressure surges, that stroke heart attack frequently happen. Although molecular components circadian rhythms rhythmically oscillate vessels, evidence a direct function "circadian clock" progression to vascular lacking.In present study, we found increased pathological remodeling injury mice...
Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower PCOS patients control subjects IR. We examined role miRNAs, particularly regulation GLUT4, insulin-sensitive transporter, AT matched subjects. was determined a...
Understanding, prioritizing, and mitigating methane (CH
The balance of nitric oxide (·NO) and superoxide anion (O⨪2) plays an important role in vascular biology. association heat shock protein 90 (Hsp90) with endothelial nitric-oxide synthase (eNOS) is a critical step the mechanisms by which eNOS generates ·NO. As capable generating both ·NO O⨪2, we hypothesized that Hsp90 might also mediate eNOS-dependent O⨪2 production. To test this hypothesis, bovine coronary cells (BCEC) were pretreated geldanamycin (GA, 10 μg/ml; 17.8 μm) then stimulated...
We tested the hypothesis that nitric oxide (NO) inhibits endothelium-derived hyperpolarizing factor (EDHF)-induced vasodilation via a negative feedback pathway in coronary microcirculation. Coronary microvascular diameters were measured using stroboscopic fluorescence microangiography. Bradykinin (BK)-induced dilation was mediated by EDHF, when NO and prostaglandin syntheses inhibited, or EDHF blocked. Specifically, BK (20, 50, 100 ng. kg(-1). min(-1) ic) caused dose-dependent similarly...
Pulmonary hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PAs) resulting in high blood pressure ultimately right ventricular failure. Elevated production reactive oxygen species by NADPH oxidase 4 (Nox4) associated with increased PH. However, the cellular location Nox4 its contribution to aberrant vascular PH remains poorly understood. Therefore, we sought identify cells expressing PAs determine functional relevance PH.Elevated...
Diabetes is the leading cause of kidney failure, accounting for >45% new cases dialysis. Diabetic nephropathy characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator diseases, but recent studies dispute these findings suggest can favorably modulate inflammation. Here, we examined role in diabetic nephropathy. We observed levels plasma urine were...
BACKGROUND: Although combination antiretroviral therapy has increased life expectancy in people living with HIV, it led to a marked increase the prevalence of hypertension, cause which is unknown. Despite therapy, HIV-derived proteins remain expressed and produced by CD4 + T lymphocytes HIV. However, their contribution HIV-associated hypertension impaired endothelium-dependent relaxation remains ill defined. METHODS: Here, we tested hypothesis that cells expressing viral contribute...
This study determined alterations to nitric oxide (NO)-dependent dilation of skeletal muscle arterioles from obese (OZR) versus lean Zucker rats (LZR). In situ cremaster both groups were viewed via television microscopy, and vessel was measured with a video micrometer. Arteriolar acetylcholine sodium nitroprusside reduced in OZR LZR, although aprikalim unaltered. NO-dependent flow-induced arteriolar (via parallel microvessel occlusion) attenuated OZR, impairing ability regulate wall shear...
Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected long-term monitoring telemetry age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171±10 versus 120±10 mg/dL), insulin (1.8±0.5 0.7±0.1 μg/L), and...
The risk of cerebrovascular disease is four- to sixfold higher in patients with diabetes. Vascular remodeling, characterized by extracellular matrix deposition and an increased media-to-lumen ratio, occurs diabetes contributes the development complications. However, diabetes-induced changes structure remain unknown. Endothelin-1 (ET-1), a potent vasoconstrictor profibrotic properties, chronically elevated To determine diabetes-mediated cerebrovasculature role ET-1 this process, type 2...
Rationale: Disruption of the circadian clock in mice produces vascular dysfunction as evidenced by impairments endothelium-dependent signaling, vasomotion, and blood vessel remodeling. Although altered function endothelial NO synthase overproduction reactive oxygen species are central to endothelium, date, impact on coupling production is not known. Objective: The goals present study were determine whether deletion a critical component clock, Bmal1, can influence levels arteries from...
Objectives— Increased formation of reactive oxygen species (ROS) has been identified as a causative factor in endothelial dysfunction by reducing NO bioavailability and uncoupling nitric oxide synthase (eNOS). However, the specific contribution ROS to function is not well understood. Methods Results— A major source intracellular NADPH oxidase (Nox) family enzymes. The goal current study was directly assess derived superoxide eNOS expressing Nox5, single gene product that constitutively...
Although the anorexic effects of leptin are lost in obesity, leptin-mediated sympatho-activation is preserved. The cardiovascular consequences obesity poorly understood. We tested hypothesis that 32 weeks high-fat diet (HFD) induces metabolic resistance but preserves system. HFD mice significantly increased body weight and plasma concentrations reduced leptin. heart rate, stroke volume, cardiac output, aldosterone levels not blood pressure. As reflected by contractile response to...
NADPH oxidase5 (Nox5) is a novel Nox isoform which has recently been recognized as having important roles in the pathogenesis of coronary artery disease, acute myocardial infarction, fetal ventricular septal defect and cancer. The activity Nox5 production reactive oxygen species regulated by intracellular calcium levels phosphorylation. However, kinases that phosphorylate remain poorly understood. Previous studies have shown phosphorylation PKC dependent, but this contention was based on use...
Excessive reactive oxygen species contribute to vascular dysfunction. We have previously shown that heat shock protein (Hsp90) inhibitors potently suppress Nox 1 3 and 5, the goals of this study were identify how molecular chaperones regulate function.In vitro, expression 2, 5 was decreased by Hsp90 in multiple cell types (human pulmonary artery endothelial cells, neutrophils, macrophages, human saphenous vein). In mice treated with inhibitors, Nox1 reduced lung along from leukocytes....
Arginase can cause vascular dysfunction by competing with nitric oxide synthase for l-arginine and increasing cell proliferation collagen formation, which promote fibrosis/stiffening. We have shown that increased arginase expression/activity contribute to endothelial (EC) dysfunction. Here, we examined the roles of two isoforms, I II (AI AII, respectively), in this process. Experiments were performed using streptozotocin-induced diabetic mice: wild-type (WT) mice knockout lacking AII isoform...
The expression and functional significance of NADPH oxidase 5 (Nox5) its five isoforms in vascular cells is poorly understood. goal this study was to determine whether Nox5-α, -β, -δ, -γ, -ε (short) are expressed human blood vessels evaluate their respective functions. Nox5 mRNA protein were detected vessels, cultured smooth muscle (HVSMC) endothelium, but not fibroblasts. most abundant α β, whereas δ γ detected. Nox5-α -β produced reactive oxygen species (ROS), catalytically active....
A defining characteristic of pulmonary hypertension (PH) is the extensive remodeling arteries (PAs), which results in progressive increases vascular resistance and stiffness eventual failure right ventricle. There no cure for PH identification novel molecular mechanisms that underlie increased proliferation, reduced apoptosis, excessive extracellular matrix production artery smooth muscle cells (PASMCs) a vital objective. Galectin-3 (Gal-3) chimeric lectin potent driver many aspects...
This study examined skeletal muscle microvessel reactivity to constrictor stimuli in obese (OZR) versus lean Zucker rats (LZR). Gracilis arteries from both rat groups were isolated, cannulated with glass micropipettes, and viewed via television microscopy. Changes vessel diameter measured a video micrometer. Arterial constriction norepinephrine was elevated OZR LZR, although vasoconstrictor endothelin angiotensin II unaltered. Differences between vessels of LZR not explained by the loss...
Background —Physical forces, such as pressure and flow, are well known to affect vascular function in the coronary circulation. Increases shear stress produce vasodilation arterioles vitro, constant-flow preparations suggest a role for stress–induced during adjustments metabolic demand vivo. Hypothetically, regulation of can be viewed negative feedback control scheme (increased velocity → increased decreased normalized). Therefore, we hypothesized that would at least partially regulated...
Responses of epicardial coronary arterioles to ACh were measured using stroboscopic fluorescence microangiography in dogs ( n = 38). (0.1 and 0.5 μg ⋅ kg −1 min ic) dilated small (<100 μm, 11 ± 2 19 2%, respectively) large (>100 6 3 13 3%, at baseline. Combined administration N ω -monomethyl-l-arginine (l-NMMA; 1.0 μmol/min indomethacin (10 mg/kg iv) eliminated ACh-induced dilation but only partially attenuated that arterioles. Suffusion a buffer containing 60 mM KCl (high KCl)...
This study characterized myogenic activation of skeletal muscle (gracilis) resistance arteries from lean (LZR) and obese Zucker rats (OZR). Arteries OZR exhibited increased versus LZR; this increase was impaired by endothelium denudation or nitric oxde synthase inhibition. Treatment vessels with 17-octadecynoic acid responses in both strains comparable amounts. Dihydroethidine microfluorography indicated elevated vascular superoxide levels immunohistochemistry demonstrated nitrotyrosine OZR,...