STUDIES OF ENDOTHELIUM IN RELATION TO ATHEROGENESIS

内吞作用，细胞外大分子的捕获和内化 囊泡来源于细胞表面的内陷，存在于所有哺乳动物身上。 细胞。内吞物质在细胞内的去向似乎主要是 在细胞的溶酶体系统中降解。然而，在某些情况下， 很大比例的囊泡不与溶酶体融合，而是排出细胞。 通过反向内吞作用。这发生在动脉内皮细胞中，因此 起到阻止血液中大分子通过的动态屏障的作用 进入动脉壁。因此，大分子的跨内皮通量 脂蛋白受内吞作用的调节。动脉局灶性增生症 平滑肌细胞(SMC)和脂蛋白-脂质堆积是一种特征 动脉粥样硬化形成的特点。因此，内吞作用的控制假定 脂蛋白及其后续经内皮细胞转运的重要性 SMC的内部化。关于正常的控制，我们知之甚少 内吞作用。因为动脉粥样硬化的形成与生长特性的改变有关 关于内皮和SMC，该项目旨在研究两者之间的关系 培养血管生长与定量脂蛋白内吞作用的关系 血管内皮细胞和SMC。低密度脂蛋白的内吞速率 通过几条途径将在静止和生长的血管细胞中进行测量。 增长状况将在一定程度上受到特定增长因素的影响。这个 研究将扩大到包括对低密度脂蛋白收费的影响的调查 在囊泡细胞选择性进入和降解时。量化数据： 内吞作用的控制将与多种假定的机制有关。 动脉粥样硬化的形成。

Endocytosis, the capture and internalization of extracellular macromolecules in vesicles derived from invagination of the cell surface, occurs in all mammalian cells. The intracellular fate of the endocytosed substances appears mainly to be degradation in the lysosomal system of the cell. In some cases however, a large proportion of vesicles do not fuse with lysosomes but pass out of the cell by reverse endocytosis. This occurs in the arterial endothelium which therefore functions as a dynamic barrier to the passage of macromolecules from the blood into the artery wall. Thus transendothelial flux of macromolecules such as lipoproteins is regulated by endocytosis. Focal proliferation of arterial smooth muscle cells (SMC) and lipoprotein-lipid accumulation is a characteristic feature of atherogenesis. Therefore, the control of endocytosis assumes importance in transendothelial transport of lipoproteins and their subsequent internalization in SMC. Little is known concerning normal control of endocytosis. Because atherogenesis is associated with altered growth properties of endothelium and SMC, the project is designed to investigate the relationships between growth and quantitative lipoprotein endocytosis in cultured vascular endothelium and SMC. The rates of endocytosis of low density lopoproteins (LDL) via several pathways will be measured in quiescent and growing vascular cells. Growth status will be manipulated in part by specific growth factors. The studies will be extended to include investigations of the effects of LDL charge upon selective entry and degradation in vescular cells. Quantitative data on control of endocytosis will be related to various postulated mechanisms of atherogenesis.