ROLE OF PLASMA LIPOPROTEINS IN ATHEROSCLEROSIS

这项拟议的研究的目标是确定 血浆脂蛋白在脂类细胞外蓄积中的作用 动脉和大动脉。我们的努力方向将是 影响卵磷脂活性的因素研究 胆固醇酰基转移酶脂转移蛋白及其性质 它们参与了新陈代谢和运输 循环中的胆固醇和胆固醇酯。自.以来 酶促反应可能促进游离态的转移 从主动脉组织中的胆固醇到高密度脂蛋白， 酶是预防脂肪的一个潜在的重要因素 积累。酶促反应产生的胆固醇酯 反应在不同等离子体之间迅速平衡 脂蛋白是通过脂转移蛋白实现的。因此，一个紧密的功能 酶和该载体之间存在相互关系 蛋白质决定胆固醇在循环中的命运。 我们将试图澄清：1)各种因素的影响 卵磷脂-胆固醇酰基转移酶中的载脂蛋白 反应，2)脂转移蛋白的性质及其相互作用 与血浆脂蛋白和脂质颗粒的相互作用，3) 影响胆固醇形成和分布的因素 血浆中的酯；4)高密度脂蛋白的肝脏代谢 胆固醇酯和甘油三酯。第一阶段的研究是 以提供有关该病毒的分子机制的基本信息 不同品种对酶反应的激活和抑制作用 载脂蛋白。第二阶段的研究涉及 脂转移蛋白的特性及其性质 与血浆脂蛋白的相互作用。在第三阶段的研究中， 酶与脂类转移的相互关系 我们将强调人们的反应。最后一阶段的研究将 研究肝脏对产生的胆固醇酯的摄取 通过卵磷脂-胆固醇酰基转移酶和残留在高密度脂蛋白中，AS 和甘油三酯的裂解转移到高密度脂蛋白 肝甘油三酯脂肪酶。人类血浆将主要用于 用于分离卵磷脂-胆固醇酰基转移酶、脂类 转运蛋白和血浆脂蛋白。肝病 高密度脂蛋白胆固醇酯和甘油三酯的代谢 大鼠肝脏灌流和培养的实验研究 肝细胞。通过拟议的研究，我们希望制定出 说明卵磷脂-胆固醇作用的详细方案 酰基转移酶与脂转移蛋白在细胞转运中的作用 胆固醇从外周组织到肝脏。

The goal of the proposed research is to determine the role of plasma lipoproteins in the extracellular accumulation of lipids in the arteries and aorta. Our efforts will be directed toward the study of the factors influencing the activities of lecithin- cholesterol acyltransferase lipid transfer protein and the nature of their involvement in the metabolism and transport of cholesterol and cholesterol esters in the circulation. Since the enzymatic reaction may facilitate the transfer of free cholesterol from aortic tissues to high density lipoproteins, the enzyme is potentially an important factor in preventing lipid accumulation. The cholesterol esters produced by the enzymatic reaction are rapidly equilibrated among various plasma lipoproteins by lipid transfer protein. Thus, a close functional interrelationship exists between the enzyme and this carrier protein in determining the fate of cholesterol in the circulation . We will attempt to clarify: 1) the effects of various apolipoproteins in the lecithin-cholesterol acyltransferase reaction, 2) the properties of lipid transfer protein and its interaction with plasma lipoproteins and lipid particles, 3) the factors influencing the formation and distribution of cholesterol esters in plasma, and 4) the hepatic metabolism of HDL cholesterol esters and triglycerides. The first phase of study is to provide basic information on the molecular mechanisms of the activation and inhibition of the enzymatic reaction by various apolipoproteins. The second phase of study is concerned with the characterization of lipid transfer protein and the nature of its interaction with plasma lipoproteins. In the third phase of study, the interrelationship of the enzymatic and lipid transfer reactions will be emphasized. The last phase of study will investigate the hepatic uptake of the cholesterol esters produced by lecithin-cholesterol acyltransferase and remaining in HDL, as well as the cleavage of the triglycerides transferred to HDL by hepatic triglyceride lipase. Human plasma will be primarily used for the separation of lecithin-cholesterol acyltransferase, lipid transfer protein, and plasma lipoproteins. The hepatic metabolism of HDL cholesterol esters and triglycerides will be investigated by using perfused rat liver and cultured rat hepatocytes. Through the proposed study, we hope to formulate a detailed scheme illustrating the roles of lecithin-cholesterol acyltransferase and lipid transfer protein in the transport of cholesterol from peripheral tissues to the liver.