STUDIES OF ENDOTHELIUM IN RELATION TO ATHEROGENESIS

内皮与动脉粥样硬化相关的研究

• 批准号: 3350597
• 负责人: Peter Francis Davies
• 金额: $ 22.03万
• 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/3350597
• 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.

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，发生在所有哺乳动物中， 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降解。 然而，在某些情况下， 大部分囊泡不与溶酶体融合，而是从细胞中排出 通过反向内吞作用。 这发生在动脉内皮，因此 作为一种动态屏障阻止大分子从血液中通过 刺入动脉壁 因此，大分子如 脂蛋白受内吞作用调节。 动脉局灶性增生 平滑肌细胞（SMC）和脂蛋白脂质积聚是一个特征 动脉粥样硬化的特征。 因此，内吞作用的控制假设 脂蛋白跨内皮转运及其后续 SMC的内在化。 关于正常的控制知之甚少， 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 本课题旨在探讨血管内皮细胞与平滑肌细胞的关系， 在培养的血管中生长和定量脂蛋白内吞之间的关系 内皮细胞和SMC。 低密度脂蛋白（LDL）的内吞率 将在静止和生长的血管细胞中测量通过几种途径的表达。 生长状态将部分由特定的生长因子操纵。 的 研究将扩展到包括LDL电荷影响的调查 在选择性进入和在囊泡细胞中降解后。 的定量数据 内吞作用的控制将与各种假定的内吞作用机制有关。 动脉粥样硬化