STUDIES OF ENDOTHELIUM IN RELATION TO ATHEROGENESIS

内吞作用，细胞外大分子的捕获和内化

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.