ANTIATHEROGENIC EFFECTS OF MODERATE ALCOHOL USE

申请人摘要：冠状动脉粥样硬化是导致 在美国，女性和男性的死亡率都很高。 几项流行病学 研究发现， 适度饮酒的人 据了解，许多消费者 即使是少量的酒精也会增加血浆总水平， 密度脂蛋白（HDL）。 这种效应可以介导至少一部分 酒精对心血管死亡率的影响，因为众所周知， 高密度脂蛋白水平与低风险相关。 这个项目是 旨在阐明适度饮酒对 高密度脂蛋白及其在分子水平上的抗动脉粥样硬化作用。 先前 试图理解这些影响的努力受到了阻碍， 迄今为止用于分离HDL物质的方法，即 已经发现超离心破坏了它们的结构， 不能有效地研究。 该项目将利用主要 免疫吸附技术的进展， 酒精对HDL的天然分子种类，避免 超离心，并将评估对两种抗动脉粥样硬化药物的影响。 HDL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.