PLASMA LIPOPROTEINS AND ATHEROSCLEROSIS

这项研究的目的是确定 血浆脂蛋白在细胞外积累的脂质， 动脉和主动脉 我们的努力将针对 影响卵磷脂活性因素的研究 胆固醇酰基转移酶和脂质转移蛋白的性质 它们参与了代谢和运输 胆固醇和胆固醇酯在循环中。 以来 酶促反应可以促进游离的 胆固醇从主动脉组织到高密度脂蛋白， 酶是预防脂质过氧化的潜在重要因素 积累 胆固醇酯是由酶催化产生的， 反应在各种等离子体之间迅速平衡 脂蛋白通过脂质转移蛋白。 因此，一个封闭的函数 酶与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对脂质转运的影响。 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，和4）HDL的肝脏代谢 胆固醇酯和甘油三酯。 研究的第一阶段是 提供有关的分子机制的基本信息 通过各种方法激活和抑制酶促反应， 载脂蛋白 第二阶段的研究涉及 脂质转运蛋白的特性及其性质 与血浆脂蛋白的相互作用。 在研究的第三阶段， 酶和脂质转移的相互关系 反应将被强调。 研究的最后阶段将 研究肝脏对所产生的胆固醇酯的摄取 通过卵磷脂胆固醇酰基转移酶和剩余的HDL， 以及甘油三酯的裂解转移到HDL， 肝甘油三酯脂肪酶 人血浆将主要用于 用于分离卵磷脂-胆固醇酰基转移酶、脂质 转运蛋白和血浆脂蛋白。 肝 高密度脂蛋白胆固醇酯和甘油三酯的代谢将 用大鼠肝脏灌流和培养的大鼠 肝细胞 我们希望透过这项研究， 详细说明卵磷脂-胆固醇的作用 酰基转移酶和脂质转移蛋白在运输 胆固醇从外周组织转移到肝脏。

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.