OXIDATIVE STRESS, ANTIOXIDANTS AND EDRF ACTION

这一建议是基于这样一个假设，即抗氧化剂限制了 冠状动脉粥样硬化性心脏病的临床表现 保存EDRF动作。EDRF活动异常在早期发展 动脉粥样硬化，部分与局部血管过多有关。 氧化应激与氧化型低密度脂蛋白的蓄积 (低密度脂蛋白)。本申请中提供的最新研究和初步数据 强烈地表明氧化应激和 血管壁中的抗氧化防御有助于血管的发展 EDRF活动受损。总体目标是研究 抗氧化剂的常驻血管细胞含量所提供的保护 关于细胞介导的低密度脂蛋白氧化，细胞产生的 活性氧物种，如超氧阴离子和过氧化氢， 以及保护EDRF的作用，以回应氧化侮辱。 这一提议的主要实验模型将是培养的牛 主动脉内皮细胞和平滑肌细胞。这些因素的相关性 将使用一种新的模型来评估体内低密度脂蛋白氧化的影响 低密度脂蛋白被完整的动脉段氧化。我们的研究将确定 这些抗氧化剂对细胞产生反应性的影响 氧物种，如超氧阴离子和过氧化氢，并开始 对造成这些影响的机制进行调查(S)。在……里面 特别是，这些对超氧化物和氢的影响的关系 抗氧化剂介导的过氧化产物对低密度脂蛋白氧化和 将研究EDRF的作用。我们将研究血管的作用 抗氧化剂含量在保存EDRF时对多种反应的反应 氧化损伤，包括活性氧和氧化型低密度脂蛋白。这个 本提案中包含的工作将提供对 抗氧化剂对慢性阻塞性肺疾病患者的作用机制(S) 动脉硬化。特别是，这项工作将有助于确立 血管抗氧化剂含量在保存重要动态平衡中的作用 局部血管EDRF作用等功能。

This proposal is based on the hypothesis that antioxidants limit the clinical manifestations of coronary artery disease in patients by preserving EDRF action. Abnormalities of EDRF action develop early in atherosclerosis and are related, in part, to excess local vascular oxidative stress and accumulation of oxidized low-density lipoprotein (LDL). Recent studies and preliminary data presented in this application strongly suggest that an imbalance between oxidative stress and antioxidant defenses in the vascular wall contribute to the development of impaired EDRF action. The overall objectives are to examine the protection afforded by the resident vascular cell content of antioxidants with respect to cell-mediated LDL oxidation, the cellular production of reactive oxygen species such as superoxide anion and hydrogen peroxide, and the preservation of EDRF action in response to oxidative insult. The primary experimental model for this proposal will be cultured bovine aortic endothelial and smooth muscle cells. The relevance of these effects for LDL oxidation in vivo will be assessed using a new model of LDL oxidation by intact arterial segments. Our research will determine the effects of these antioxidants on cellular production of reactive oxygen species such as superoxide anion and hydrogen peroxide and begin investigation into the mechanism(s) responsible for these effects. In particular, the relationship of these effects on superoxide and hydrogen peroxide production with antioxidant-mediated effects on LDL oxidation and EDRF action will be studied. We will investigate the role of vascular antioxidant content in preserving EDRF action in response to a variety of oxidative insults including reactive oxygen species and oxidized LDL. The work contained in this proposal will provide new insights into the mechanism(s) by which antioxidants provide benefit for patients with atherosclerosis. In particular, this work will help establish the role of vascular antioxidant content in the preservation of important homeostatic functions such as local vascular EDRF action.