Exercise training: Endothelial phenotype, CAD

运动训练：内皮表型、CAD

• 批准号: 6592193
• 负责人: M HAROLD LAUGHLIN
• 金额: $ 24.72万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-13 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592193
• 关键词: blood flow measurement; coronary disorder; dietary lipid; disease /disorder model; environmental adaptation; exercise; heart circulation; hemodynamics; hyperlipidemia; immunocytochemistry; miniature swine; nitric oxide synthase; nutrition related tag; pathogenic diet; phenotype; prostaglandin endoperoxide synthase; shear stress; substance P; vascular endothelium; vascular resistance; vasodilators; vasomotion

Exercise training (EX) induces enhanced endothelium-mediated vasodilation in coronary arterioles in part by increasing endothelial nitric oxide synthase (ecNOS). Endothelium-mediated vasodilation is a complex phenomenon. It appears that increased ecNOS expression is only one mechanism for improved endothelial function. Project 3 will accomplish 4 specific aims and examine endothelium throughout the coronary arterial tree because EX-induced adaptations appear to occur non-uniformly. Aim 1 will test 3 hypothesized mechanisms for improved endothelium-mediated dilation: a) Increased production of PGI/2 via the cyclooxygenase (COX-1); b) Increased expression of cytochrome P450WC11; and c) increased effectiveness of NO due to antioxidant systems. Endothelium function will be measured and pharmacologic, biochemical, and molecular approaches will define expression for enzymes/receptors. Aim 2 will test the hypothesis that shear stress and distention are signals for altered endothelial phenotype in isolated arterioles. Aim 3 is designed to examined endothelial phenotype in arteries of specified size. We propose that endothelial phenotype (and EX-induced changes in endothelial phenotype) in the coronary arterial tree is partially determined by shear stress and wall distention. Aim 4 will test mechanisms hypothesized to be responsible for the ability of EX to restore endothelial function of coronary arteries during hyperlipidemia (HF). Vasomotor responses and biochemical/molecular characterization of endothelial cell phenotype will be used to test the hypothesis that EX reverses HF-induced endothelial dysfunction in coronary arteries through increased expression of ecNOS, COX-1, P450 2C11 isozyme, and/or antioxidant systems. The proposed research will ascertain mechanisms of EX-induced enhancement of endothelial function in coronary arteries and the importance of: 1) arterial diameter, 2) shear stress, and 3) circumferential wall stress (distention). We will also determine mechanisms for effects of EX on endothelial dysfunction during HF. Results will allow integration of these important phenomena in understanding of fundamental processes in vascular adaptation in the coronary circulation. EX-induced improvements in endothelial function may be of central importance to the beneficial effects of exercise training in prevention and treatment of CHD.

运动训练(EX)通过增加内皮型一氧化氮合酶(EcNOS)诱导冠状动脉微动脉内皮细胞介导的血管扩张增强。内皮细胞介导的血管扩张是一种复杂的现象。看来，ecNOS表达增加只是改善内皮功能的一个机制。项目3将实现4个特定的目标，并检查整个冠状动脉树的内皮细胞，因为EX诱导的适应似乎发生得不均匀。目的1将测试改善内皮介导的扩张的3种假想机制：a)通过环氧合酶(COX-1)增加PGI/2的产生；b)增加细胞色素P450WC11的表达；以及c)由于抗氧化系统增加NO的有效性。内皮功能将被测量，药理学、生化和分子方法将定义酶/受体的表达。目的2将验证切应力和扩张是分离小动脉内皮细胞表型改变的信号的假设。AIM 3旨在检测特定大小动脉的内皮表型。我们认为冠状动脉树内皮细胞表型(以及外源性内皮细胞表型的改变)部分由切应力和管壁扩张决定。目的4将测试高脂血症(HF)期间EX恢复冠状动脉内皮功能的机制。血管运动反应和内皮细胞表型的生化/分子特征将被用来检验这一假说，即EX通过增加ecNOS、COX-1、P450 2C11同工酶和/或抗氧化系统的表达来逆转HF引起的冠状动脉内皮功能障碍。这项拟议的研究将确定EX诱导冠状动脉内皮功能增强的机制，以及以下因素的重要性：1)动脉内径，2)切应力，3)周壁应力(扩张)。我们还将确定EX在心力衰竭期间对内皮功能障碍的影响机制。这些结果将使我们能够整合这些重要现象，以了解冠状循环中血管适应的基本过程。运动训练对预防和治疗冠心病的有益作用可能与运动诱导的内皮功能改善有关。