APOLIPOPROTEIN E DEFICIENCY AND ATHEROSCLEROSIS

载脂蛋白 E 缺乏与动脉粥样硬化

• 批准号: 3356389
• 负责人: RANDALL W DAVIS
• 金额: $ 6.96万
• 依托单位: SEA WORLD 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: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356389
• 关键词: Cetacea; Pinnipedia; antihypercholesterolemic agent; apolipoproteins; atherosclerosis; blood lipoprotein metabolism; cardiovascular disorder prevention; coronary disorder; dietary lipid; gene expression; hyperlipidemia; malnutrition; marine animal oil; marine biology; membrane structure; omega 3 fatty acid; radiotracer; tissue /cell culture; triglycerides

In humans, apolipoprotein E (apoE) deficiency causes hyperlipidemia and vascular disease. We have recently determined that harbor seals and sea lions do not have detectable levels of plasma apoE, yet they do not develop hyperlipidemia or remnant lipoproteins typically seen in apoE deficient humans. The diet of seals and sea lions is rich in omega-3 fatty acids and may suppress VLDL synthesis, thus "masking" the impact of the apoE deficiency. The objectives of this study are 1) to determine the basis for the apoE deficiency in harbor seals and sea lions, 2) to determine the mechanism by which seals efficiently metabolize triglyceride-rich lipoproteins, and 3) to determine the role of dietary omega-3 fatty in maintaining normolipemia. First, we will determine which apoprotein(s) are responsible for receptor-mediated uptake of seal lipoproteins using both cell culture techniques and in vivo turnover studies. Second, experiments will be conducted to determine whether harbor seals and sea lions have the apoE gene and apoE mRNA using Southern and Northern blotting techniques. respectively. Third, we will assess the role of the fish-diet by feeding seals an alternative isocaloric diet high in cholesterol and saturated fat. These studies of lipoprotein metabolism are unique in that harbor seals and sea lions are animal models in which the full impact of apoE deficiency can be studied. Because their diets are composed entirely of fish, they offer a unique opportunity to determine the maximal effect of such a diet, especially in the face of apoE deficiency. Thus these studies are highly relevant to the goal of understanding the relationship of diet and lipoprotein metabolism to the causation of atherosclerosis in man.

在人类中，载脂蛋白E （apoE）缺乏引起高脂血症