ANTIATHEROGENIC EFFECTS OF MODERATE ALCOHOL USE

申请人摘要：冠状动脉粥样硬化是冠心病的主要原因 在美国，女性和男性的死亡都是如此。几种流行病学 研究发现，人们死于冠状动脉疾病的死亡率降低 适度饮酒的人。众所周知，许多消费的个人 即使是少量的酒精也会增加血浆总水平 密度脂蛋白(HDL)。这一效应可能至少在一定程度上 酒精对心血管死亡率的影响是众所周知的 高密度脂蛋白水平越高，风险越低。这个项目是 旨在阐明适度饮酒对健康的影响 高密度脂蛋白及其在分子水平的抗动脉粥样硬化作用。上一首 理解这些影响的努力受到了以下事实的阻碍： 迄今用于分离高密度脂蛋白物种的方法，即 超速离心，已经被发现破坏了他们的结构，以至于 它们不能被有效地研究。这个项目将利用主要的 允许测量效应的免疫吸附技术的进展 酒精对天然高密度脂蛋白分子物种的影响，避免 超速离心法，并将评估两种抗动脉粥样硬化的效果 高密度脂蛋白的功能，抑制低密度脂蛋白的氧化， 以及从细胞中回收胆固醇。这些研究的结果 将在制定公共卫生政策方面发挥重要作用 适度饮酒的相对益处和风险。

APPLICANT'S ABSTRACT: Coronary atherosclerosis is the leading cause of death in the United States in both women and men. Several epidemiologic studies have found decreased mortality from coronary disease among people who use alcohol moderately. It is known that many individuals who consume alcohol even in small amounts have increased levels of total plasma high density lipoproteins (HDL). This effect may mediate at least a portion of the effect of alcohol on cardiovascular mortality because it is well known that higher levels of HDL are associated with lower risk. This project is directed at elucidation of the effects of moderate alcohol consumption on HDL and its antiatherogenic functions at the molecular level. Previous attempts to understand these effects have been impeded by the fact that the method heretofore employed to separate HDL species, i.e. ultracentrifugation, has been found to disrupt their architecture such that they cannot be effectively studied. This project will exploit major advances in immunosorption techniques that permit measurement of the effects of alcohol on the native molecular species of HDL, avoiding ultracentrifugation, and will assess the effects on two antiatherogenic functions of HDL, the inhibition of oxidation of low density lipoproteins, and the retrieval of cholesterol from cells. The results of these studies will be important in establishing public health policy with respect to the relative benefits and risks of moderate alcohol consumption.