REDOX STATUS AND ANTIOXIDANTS IN PLATELET FUNCTION

描述 (改编自申请人的摘要)流行病学研究表明 抗氧化剂在预防心血管疾病中发挥作用 人类和饮食中抗氧化剂的摄入量与 冠状动脉疾病的发展。精确的机制， 然而，这些观察结果背后的原因尚不清楚。在受益的同时 抗氧化剂的作用被归因于防止氧化 低密度脂蛋白的修饰及其抑制作用 除了动脉粥样硬化的形成，其他因素也可能很重要。初步数据 这一应用表明，血小板功能依赖于 在氧化应激和抗氧化保护之间取得平衡。 在这项计划的头两年，申请人将学习 指导下的抗氧化剂生物化学和自由基化学 巴尔茨·弗雷博士，这一领域的知名研究人员。这个 申请者将参与已经在进行中的成功研究。 弗雷的实验室，并开始具体解决 即细胞内抗氧化剂状态对血小板的影响 功能和对任何观察到的效果负责的机制。在 三年后，申请者将开始一段独立的时期 进一步研究生物化学和分子效应 抗氧化剂对血小板功能的影响与这项提案的发起人Dr。 约瑟夫·洛斯卡尔佐，医学博士，博士。在此期间，申请人将：1) 膜抗氧化状态在调节血小板中的作用 2)通过以下方式确定这些发现的体内相关性 研究抗氧化剂耗尽或补充的动物模型。这项工作 本提案中包含的内容将为该机制提供新的见解(S) 通过抗氧化剂为血管疾病患者提供益处。 申请者的最终目标是继续获得下列初步数据 这个应用程序，并开发一个独立的研究程序来检查 细胞氧化还原状态、抗氧化剂和血管之间的相互作用 动态平衡。

DESCRIPTION (Adapted from the applicant's abstract) Epidemiological studies have shown that antioxidants play a role in the prevention of cardiovascular disease in humans and that dietary antioxidant consumption is inversely associated with the development of coronary artery disease. The precise mechanisms that underlie these observations, however, are not clear. While the beneficial effects of antioxidants have been attributed to the prevention of oxidative modification of low-density lipoprotein (LDL) and the inhibition of atherogenesis, other factors may also be important. Preliminary data presented in this application suggests that platelet function is dependent upon the balance between oxidative stress and antioxidant protection. In the first two years of this proposal, the applicant will study antioxidant biochemistry and free radical chemistry under the direction of Dr. Balz Frei, Ph.D., an established investigator in this field. The applicant will participate in successful research already in progress in Dr. Frei's laboratory and begin to specifically address the first aim of the proposal; namely, the effect of cytosolic antioxidant status on platelet function and the mechanisms responsible for any observed effects. In the latter three years the applicant will begin a period of independent investigation further examining the biochemical and molecular effects of antioxidants on platelet function with the sponsor of this proposal, Dr. Joseph Loscalzo, M.D., Ph.D. During this period, the applicant will: 1) characterize the role of membrane antioxidant status in modulating platelet function and 2) determine the in vivo relevance of these findings by studying an antioxidant-depleted or - supplemented animal model. The work contained in this proposal will provide new insights into the mechanism(s) by which antioxidants provide benefit for patients with vascular disease. The applicant's ultimate goal is to pursue the preliminary data presented in this application and develop an independent research program examining the interaction between cellular redox status, antioxidants, and vascular homeostasis.