STUDIES OF ENDOTHELIUM IN RELATION TO ATHEROGENESIS

内皮与动脉粥样硬化相关的研究

• 批准号: 3350601
• 负责人: Peter Francis Davies
• 金额: $ 24.01万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1987-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3350601
• 关键词: atherosclerosis; autoradiography; blood lipoprotein metabolism; cell morphology; cell population study; cell type; electron microscopy; growth factor; human tissue; low density lipoprotein; membrane activity; pinocytosis; radiotracer; receptor mediated endocytosis; simian virus 40; tissue /cell culture; transforming virus; vascular endothelium; vascular smooth muscle

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.

胞吞作用，细胞外大分子的捕获和内化 源自细胞表面内陷的囊泡，存在于所有哺乳动物中 细胞。 内吞物质的细胞内命运似乎主要是 在细胞的溶酶体系统中被降解。 然而，在某些情况下， 大部分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 作为血液中大分子通过的动态屏障 进入动脉壁。 因此，大分子的跨内皮通量，例如 脂蛋白受内吞作用调节。 动脉局灶性增生 平滑肌细胞（SMC）和脂蛋白脂质积累是一个特征 动脉粥样硬化形成的特征。 因此，内吞作用的控制假设 脂蛋白跨内皮转运的重要性及其后续 SMC 内化。 对于正常控制知之甚少 内吞作用。 因为动脉粥样硬化与生长特性改变有关 该项目旨在研究内皮细胞和 SMC 之间的关系 培养血管中生长与定量脂蛋白内吞作用之间的关系 内皮细胞和平滑肌细胞。 低密度脂蛋白（LDL）的内吞率 将通过多种途径在静止和生长的血管细胞中进行测量。 生长状态将部分受到特定生长因子的操纵。 这 研究范围将扩大到包括 LDL 电荷影响的调查 在囊泡细胞中选择性进入和降解。 定量数据 内吞作用的控制将与各种假设的机制有关 动脉粥样硬化。