NUTRIENT ANTIOXIDANT DEFENSE OF HIGH DENSITY LIPOPROTEIN

描述(改编自申请人的摘要)：累积接触 活性氧物种已被认为是导致 衰老的退行性疾病。Low的氧化作用假说 密度脂蛋白(LDL)是动脉粥样硬化病因学的核心 心血管疾病导致了人们对低密度脂蛋白氧化的兴趣激增。 然而，尽管高密度脂蛋白(HDL)在 防止动脉粥样硬化，更容易被氧化 与低密度脂蛋白相比，对低密度脂蛋白影响的关注要少得多 氧化对高密度脂蛋白生物学特性的影响。PI的试点数据表明 饮食中的脂肪酸、抗氧化剂维生素和烟草的使用对 对高密度脂蛋白血浆浓度和氧化敏感性的影响。 PI现在将进一步检查饮食脂肪酸的影响， 抗氧化维生素和烟草使用对血浆高密度脂蛋白和高密度脂蛋白浓度的影响 低密度脂蛋白。在平行研究中，他将调查这些因素的影响。 高密度脂蛋白氧化的分子机制及营养物质的作用方式 抗氧化剂调节这些反应。具体目的是：1)学习 膳食脂肪酸、维生素E和维生素C以及吸烟对高密度脂蛋白的影响 男性和女性受试者的水平；2)研究促进剂和抗氧化剂 这些因素对高密度脂蛋白和低密度脂蛋白氧化反应的影响 从饮食修饰研究中分离出脂蛋白；3)研究 利用重组高密度脂蛋白研究高密度脂蛋白氧化和抗氧化作用的机制 含有明确的脂质、载脂蛋白和抗氧化剂的颗粒 组成。 这项提议的长期目标是阐明特定的生物 膳食促进剂和抗氧化剂对高密度脂蛋白氧化的影响。这一知识 可能对理解调节体内高密度脂蛋白水平的因素很重要。 循环，并可能建议新的饮食方法，以防止 动脉粥样硬化性心血管疾病。

DESCRIPTION (Adapted from the Applicant's Abstract): Cumulative exposure to reactive oxygen species has been proposed as a root cause of the degenerative diseases of aging. The hypothesis that oxidation of low density lipoproteins (LDL) is central to the etiology of atherosclerotic cardiovascular disease has led to an explosion of interest in LDL oxidation. However, even though high density lipoproteins (HDL) play a critical role in protecting against atherosclerosis and are more susceptible to oxidation than LDL, much less attention has been directed towards the effects of oxidation on the biological properties of HDL. The PI's pilot data suggest that dietary fatty acids, antioxidant vitamins and tobacco use have a major impact on HDL plasma concentration and oxidation susceptibility. The PI will now further examine the effects of dietary fatty acids, antioxidant vitamins and tobacco use on the plasma concentration of HDL and LDL. In parallel studies he will investigate the effects of these factors on the molecular mechanisms of HDL oxidation and the manner which nutrient antioxidants modulate these reactions. The specific aims are to: 1) study the effects of dietary fatty acids, vitamins E and C, and tobacco use on HDL levels in male and female subjects; 2) study the pro- and antioxidant effects of these factors on the oxidation reactions of HDL and LDL using lipoproteins isolated from the dietary modification studies; 3) study the mechanisms of HDL oxidation and antioxidant action using recombinant HDL particles with well-defined lipid, apolipoprotein and antioxidant composition. The long-term goal of this proposal is to elucidate the specific biologic effects of dietary pro- and antioxidants on HDL oxidation. This knowledge may be important in understanding the factors that regulate HDL levels in circulation and could suggest new dietary approaches to the prevention of atherosclerotic cardiovascular disease.