LP-A PHENOTYPE ATHEROSCLEROSIS

LP-A表型动脉粥样硬化

• 批准号: 3472075
• 负责人: David L. Rainwater
• 金额: $ 10.01万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3472075
• 关键词: Cercopithecidae; atherosclerosis; blood chemistry; blood lipoprotein; cholesterol; diet route /schedule; dietary lipid; disease /disorder proneness /risk; enzyme linked immunosorbent assay; ethanol; gene expression; genetic regulation; immunoelectron microscopy; laboratory rabbit; necrosis; nutrition related tag; protein structure

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).

高水平的脂蛋白(A)(脂蛋白(A))与更大的风险相关。 尽管人类动脉粥样硬化的确切细节 他们之间的关系是未知的。狒狒，一种灵长类动物模型 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。 我们已经开发了对Lp(A)的各个方面进行量化的技术 表型，包括血清总浓度、个体亚型 水平和脂蛋白密度。这项提案的目标是 确定Lp(A)表型与Lp(A)的关系 在恒河猴动脉粥样硬化模型上，并发展出更好的 对遗传和饮食因素的理解 Lp(A)表型。这些研究对长期发展具有重要意义 在狒狒模型中开发治疗方法的目标是 有助于降低因存在而患心血管疾病的风险 Lp(A)。这项建议有五个具体目标：1)确定 Lp(A)表型在人群中的出现频率 2)检验Lp(A)表型为 与动脉粥样硬化病变程度有关。LP(A) 320只狒狒的表型将根据程度进行评估 尸检后评估的动脉粥样硬化；3)测试 Lp(A)餐后形态与程度相关的假说 动脉粥样硬化性病变。我们会决定餐后的 Lp(A)表型(120只狒狒)，将根据关系进行评估 以达到动脉粥样硬化的程度；4)检验Lp(A) 表型对饮食有反应。Lp(A)表型将为 确定并与以下水平的持续变化相关联 100只狒狒的膳食脂肪和胆固醇。据报道，乙醇被 降低人类Lp(A)水平，我们将Lp(A)与 8只猪的表型与饲料中乙醇含量的变化 以及5)检验两个主要基因控制的假设 Lp(A)表型的不同方面 纯种殖民地的成员。了解饮食和 遗传对Lp(A)表型的影响及其与 动脉粥样硬化，将帮助我们计划降低风险的策略 由于Lp(A)的存在而引起的心血管疾病。