A5086468930- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Electron Spin Resonance Studies
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sodium Intake and Health
- Redox biology and oxidative stress
- Cardiac Ischemia and Reperfusion
- Hormonal Regulation and Hypertension
- Renin-Angiotensin System Studies
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Atherosclerosis and Cardiovascular Diseases
- Sirtuins and Resveratrol in Medicine
- Free Radicals and Antioxidants
- Cardiovascular Health and Risk Factors
- Cardiovascular Disease and Adiposity
- Lanthanide and Transition Metal Complexes
- Analytical Chemistry and Sensors
- Vitamin C and Antioxidants Research
- Esophageal Cancer Research and Treatment
- ATP Synthase and ATPases Research
- Antioxidant Activity and Oxidative Stress
- RNA modifications and cancer
- Diet and metabolism studies
Vanderbilt University Medical Center
2016-2025
University of Miami
2024
Nashville Oncology Associates
2023
Vanderbilt University
2013-2022
RELX Group (United States)
2022
Scientific Center of Family Health Problems and Human Reproduction
2021
Emory University
2003-2012
Atlanta VA Medical Center
2008-2010
Massachusetts General Hospital
2010
Cedars-Sinai Medical Center
2010
Hypertension promotes atherosclerosis and is a major source of morbidity mortality. We show that mice lacking T B cells (RAG-1−/− mice) have blunted hypertension do not develop abnormalities vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)–salt. Adoptive transfer T, but B, restored these abnormalities. Angiotensin known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in several cells,...
Tetrahydrobiopterin is a critical cofactor for the NO synthases, and in its absence these enzymes become "uncoupled," producing reactive oxygen species (ROSs) rather than NO. In aortas of mice with deoxycorticosterone acetate-salt (DOCA-salt) hypertension, ROS production from synthase markedly increased, tetrahydrobiopterin oxidation evident. Using deficient NADPH oxidase subunit p47(phox) lacking either endothelial or neuronal synthase, we obtained evidence that hypertension produces...
Tetrahydrobiopterin is a critical cofactor for the NO synthases, and in its absence these enzymes become “uncoupled,” producing reactive oxygen species (ROSs) rather than NO. In aortas of mice with deoxycorticosterone acetate–salt (DOCA-salt) hypertension, ROS production from synthase markedly increased, tetrahydrobiopterin oxidation evident. Using deficient NADPH oxidase subunit p47phox lacking either endothelial or neuronal synthase, we obtained evidence that hypertension produces cascade...
Human cardiac fibroblasts are the main source of fibrosis associated with hypertrophy and heart failure. Transforming growth factor-beta1 (TGF-beta1) irreversibly converts into pathological myofibroblasts, which express smooth muscle alpha-actin (SM alpha-actin) de novo produce extracellular matrix. We hypothesized that TGF-beta1-stimulated conversion to myofibroblasts requires reactive oxygen species derived from NAD(P)H oxidases (Nox). found TGF-beta1 potently upregulates contractile...
Rationale : Superoxide ( ) has been implicated in the pathogenesis of many human diseases including hypertension; however, commonly used antioxidants have proven ineffective clinical trials. It is possible that these agents are not adequately delivered to subcellular sites superoxide production. Objective Because mitochondria important sources reactive oxygen species, we postulated mitochondrial targeting scavenging would therapeutic benefit. Methods and Results In this study, found hormone...
Tetrahydrobiopterin (BH<sub>4</sub>) serves as a critical co-factor for the endothelial nitric-oxide synthase (eNOS). A deficiency of BH<sub>4</sub> results in eNOS uncoupling, which is associated with increased superoxide and decreased NO<sup>•</sup> production. has been suggested to be target oxidation by peroxynitrite (ONOO<sup>–</sup>), ascorbate shown preserve levels enhance production; however, mechanisms underlying these processes remain poorly defined. To gain further insight into...
Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang could induce oxidative damage in turn might decrease endothelial nitric oxide (NO · ) bioavailability promote vascular stress. The effect ROS, respiration, membrane potential, glutathione, NO was studied isolated mitochondria intact bovine aortic...
Hypertension caused by angiotensin II is dependent on vascular superoxide (O 2 ·−) production. The nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase a major source of O ·− and activated in vitro. However, its role II-induced hypertension vivo less clear. In the present studies, we used mice deficient p47 phox , cytosolic subunit NADPH oxidase, to study this enzyme system vivo. vivo, infusion (0.7 mg/kg per day for 7 days) increased systolic blood pressure from 105±2 151±6 mm Hg...
Background— Impaired flow-dependent, endothelium-mediated vasodilation (FDD) in patients with chronic heart failure (CHF) results, at least part, from accelerated degradation of nitric oxide by oxygen radicals. The mechanisms leading to increased vascular radical formation, however, remain unclear. Therefore, we determined endothelium-bound activities extracellular superoxide dismutase (ecSOD), a major antioxidant enzyme, and xanthine-oxidase, potent producing their relation FDD CHF. Methods...
Oxidative damage and inflammation are both implicated in the genesis of hypertension; however, mechanisms by which these stimuli promote hypertension not fully understood. Here, we have described a pathway hypertensive dendritic cell (DC) activation T cells, ultimately leading to hypertension. Using multiple murine models hypertension, determined that proteins oxidatively modified highly reactive γ-ketoaldehydes (isoketals) formed accumulate DCs. Isoketal accumulation was associated with DC...
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...
Oscillatory shear stress occurs at sites of the circulation that are vulnerable to atherosclerosis. Because oxidative contributes atherosclerosis, we sought determine whether oscillatory increases endothelial production reactive oxygen species and define enzymes responsible for this phenomenon. Bovine aortic cells were exposed static, laminar (15 dyn/cm 2 ), (±15 ). increased superoxide ([Formula: see text]) by more than threefold over static conditions as detected using electron spin...
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...
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...
Atrial fibrillation (AF) is associated with an increased risk of stroke due almost exclusively to emboli from left atrial appendage (LAA) thrombi. Recently, we reported that AF was endocardial dysfunction, limited the atrium (LA) and LAA manifest as reduced nitric oxide (NO*) production expression plasminogen activator inhibitor-1. We hypothesized NO* levels observed in may be superoxide (O2*-) production.After a week induced by rapid pacing pigs, O2*- acutely isolated heart tissue measured...
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,...
Rationale: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in regulation metabolic antioxidant functions which associated with cardiovascular disease factors diminish level. Objective: We hypothesized that reduced expression vascular increased protects...
Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% 65 years of age paralleling the increased incidence hypertension and metabolic conditions further inactivate because NADH (nicotinamide adenine dinucleotide, reduced form) acetyl-CoA levels. impairment reduces activity a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2) hyperacetylation.In this study, we examined whether loss increases vascular oxidative stress SOD2 hyperacetylation promotes...
Sodium accumulates in the interstitium and promotes inflammation through poorly defined mechanisms. We describe a pathway by which sodium enters dendritic cells (DCs) amiloride-sensitive channels including alpha gamma subunits of epithelial channel hydrogen exchanger 1. This leads to calcium influx via exchanger, activation protein kinase C (PKC), phosphorylation p47phox, association p47phox with gp91phox. The assembled NADPH oxidase produces superoxide subsequent formation immunogenic...