LP-A PHENOTYPE ATHEROSCLEROSIS

高水平的Lp（a）（脂蛋白（a））与更大的风险有关， 动脉粥样硬化在人类，虽然精确的细节， 关系不明。 狒狒，一种灵长类动物的模型， 脂蛋白与动脉粥样硬化相互作用的研究， Lp（a）在各方面都与人类Lp（a）相似。 我们已经开发了定量Lp（a）方面的技术， 表型，包括总血清浓度、个体亚型 水平和脂蛋白密度。 本提案的目标是 确定Lp（a）表型与 动脉粥样硬化的狒狒模型，并制定一个更好的 了解遗传和饮食因素， Lp（a）表型。 这些研究对长期的 目的是在狒狒模型中开发治疗方法， 有助于降低心血管疾病的风险， Lp（a）。 该提案有五个具体目标：1）确定 Lp（a）表型在人群中的出现频率 无关狒狒; 2）检验Lp（a）表型是 与动脉粥样硬化病变程度相关。 脂蛋白a 将对320只狒狒的表型进行评价， 尸检后评估的动脉粥样硬化; 3）测试 假设餐后形式的Lp（a）与程度有关 动脉粥样硬化病变。 我们将确定餐后 Lp（a）表型（120只狒狒），将评价其与 （4）检验Lp（a）与动脉粥样硬化程度的关系; 表型对饮食有反应。 Lp（a）表型将是 确定和相关的水平一致的变化， 100只狒狒的膳食脂肪和胆固醇。 据报道，乙醇 降低人类Lp（a）水平，我们将Lp（a） 表型与饮食乙醇量的变化， 狒狒;和5）测试的假设，两个主要基因控制 Lp（a）表型的各个方面， 一个纯种殖民地的成员 了解饮食和 Lp（a）表型的遗传影响及其与 动脉粥样硬化，将帮助我们计划策略，以减少风险， 心血管疾病由于Lp（a）的存在。

High levels of Lp(a) (lipoprotein (a)) are related to greater risk of atherosclerosis in humans, although precise details of the relationship are not known. The baboon, a primate model for research on the interaction of lipoproteins and atherosclerosis, possesses Lp (a) that is similar to human Lp (a) in every respect. We have developed techniques for quantitating aspects of Lp(a) phenotype, including total serum concentration, individual isoform levels, and the lipoprotein density. The goals for this proposal are to determine the relationship between Lp(a) phenotype and atherosclerosis in the baboon model, and to develop a better understanding of the genetic and dietary factors that mediate Lp(a) phenotype. These studies are important to the long-term objective of developing therapies in the baboon model that will help reduce the risk of cardiovascular disease due to the presence of Lp(a). This proposal has five Specific Aims: 1) determine the frequency of occurrence of Lp(a) phenotypes in a population of unrelated baboons; 2) test the hypothesis that Lp(a) phenotype is related to extent of arterial atherosclerotic lesions. Lp(a) phenotype in 320 baboons will be evaluated in relation to extent of atherosclerosis assessed following necropsy; 3) test the hypothesis that postprandial forms of Lp(a) are related to extent of atherosclerotic lesions. We will determine the postprandial Lp(a) phenotype (120 baboons) which will be evaluated in relation to extent of atherosclerosis; 4) test the hypothesis that Lp(a) phenotype is responsive to diet. Lp(a) phenotype will be determined and correlated with a consistent change in levels of dietary fat and cholesterol in 100 baboons. Ethanol is reported to decrease human Lp(a) levels, and we will correlate Lp(a) phenotype with changes in amount of dietary ethanol in eight baboons; and 5) test the hypothesis that two major genes control the various aspects of Lp(a) phenotype using samples from members of a pedigreed colony. Understanding dietary and genetic influences on Lp(a) phenotype, and its association with atherosclerosis, will help us plan strategies to reduce the risk of cardiovasular disease due to the presence of Lp(a).