NADPH Oxidase and Microvascular Dysfunction in Obesity

肥胖中的 NADPH 氧化酶和微血管功能障碍

基本信息

批准号：
8434433
负责人：
ROBERT C HICKNER
金额：
$ 43.52万
依托单位：
EAST CAROLINA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-17 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434433
关键词：
Acetylcholine Address Adhesions Aerobic Aerobic Exercise Ancillary Study Applications Grants Arteries Atherosclerosis Attenuated Biopsy Blood Vessels Blood flow Coronary Arteriosclerosis Data Development Diabetes Mellitus Disease Effectiveness Endothelium Exercise Functional disorder Generations Healthcare Human Individual Inflammation Inflammatory Intervention Lesion Link Metabolic Diseases Metabolic syndrome Methodology Microdialysis Monitor Morbidity - disease rate Muscle NADPH Oxidase Obesity Obesity associated disease Oxidative Stress Participant Patients Platelet aggregation Procedures Production Proteins Reactive Oxygen Species Regulation Rest Rodent Model Skeletal Muscle Source Thrombosis Tissues Training Training Programs United States Vascular Diseases Vascular Endothelium Vasodilation Western Blotting Xanthine Oxidase acetovanillone angiogenesis attenuation care burden diabetic improved in vivo inhibitor/antagonist interstitial monocyte mortality public health relevance sedentary vasoconstriction

项目摘要

DESCRIPTION (provided by applicant): Impaired endothelial function is observed in several disease states that are related to obesity, such as atherosclerosis, coronary artery disease, and diabetes. Oxidative stress contributes to the development of these obesity-related diseases. NADPH oxidase is a major source of oxidative stress within the vasculature, and has been linked with the Metabolic Syndrome. However, there is no clear evidence that NADPH oxidase generated oxidative stress results in endothelial dysfunction in vivo. Furthermore, the mechanism(s) of exercise training-induced improvements in endothelial function have not been determined. The objectives of this study are to determine the impact of in vivo NADPH oxidase activity on endothelial function in obese as compared to lean individuals, and to determine the mechanism of training-induced improvements in endothelial function. Our unique microdialysis methodology will allow monitoring of microvascular/endothelial function and ROS generation, as well as the administration of pharmacological agents directly into muscle. The central hypothesis of this project is that elevated NADPH oxidase activity in obese individuals will contribute to microvascular endothelial dysfunction in skeletal muscle, and that endothelial function can be improved with a 12-week aerobic interval exercise intervention through an attenuation of NADPH oxidase activity.

描述（由申请人提供）：在与肥胖相关的几种疾病状态中观察到内皮功能受损，例如动脉粥样硬化、冠状动脉疾病和糖尿病。氧化应激导致这些肥胖相关疾病的发生。 NADPH 氧化酶是脉管系统内氧化应激的主要来源，并与代谢综合征有关。然而，没有明确的证据表明NADPH氧化酶产生的氧化应激会导致体内内皮功能障碍。此外，运动训练引起的内皮功能改善的机制尚未确定。本研究的目的是确定肥胖个体与瘦个体相比体内 NADPH 氧化酶活性对内皮功能的影响，并确定训练引起的内皮功能改善的机制。我们独特的微透析方法将允许监测微血管/内皮功能和 ROS 生成，以及将药物直接施用到肌肉中。该项目的中心假设是，肥胖个体中 NADPH 氧化酶活性升高将导致骨骼肌微血管内皮功能障碍，并且通过 12 周有氧间歇运动干预，可以通过减弱 NADPH 氧化酶活性来改善内皮功能。