NADPH Oxidase and Microvascular Dysfunction in Obesity

描述（由申请人提供）：内皮功能受损可在几种与肥胖相关的疾病状态中观察到，如动脉粥样硬化、冠状动脉疾病和糖尿病。氧化应激有助于这些肥胖相关疾病的发展。NADPH氧化酶是血管内氧化应激的主要来源，与代谢综合征有关。然而，体内没有明确的证据表明NADPH氧化酶产生的氧化应激导致内皮功能障碍。此外，运动训练诱导内皮功能改善的机制尚未确定。本研究的目的是确定体内NADPH氧化酶活性对肥胖人群内皮功能的影响，并确定训练诱导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，以及直接进入肌肉的药理学药物管理。该项目的中心假设是肥胖个体NADPH氧化酶活性升高将导致骨骼肌微血管内皮功能障碍，内皮功能可以通过12周的有氧间歇运动干预，通过降低NADPH氧化酶活性来改善。

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.