REGULATION OF CHOLESTEROL IN VASCULAR ENDOTHELIUM

血管内皮胆固醇的调节

• 批准号: 3337360
• 负责人: DENIS J GOSPODAROWICZ
• 金额: $ 13.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337360
• 关键词: HMG coA reductases; adrenal glands; apolipoproteins; atherosclerosis; blood lipoprotein; blood lipoprotein transport; cell differentiation; cholesterol; contact inhibition; corneal endothelium; fluorescence microscopy; fluorescent dye /probe; high density lipoproteins; human tissue; liposomes; low density lipoprotein; membrane activity; ovary; phosphatidylcholines; phospholipids; pinocytosis; radioimmunoassay; radiotracer; receptor mediated endocytosis; tissue /cell culture; ultracentrifugation; vascular endothelium; vascular smooth muscle

The mechanisms through which HDL promotes the proliferation of vascular endothelial cells will be analyzed. The physical process of binding, internalization, and degradation of HDL and HDL subclasses will be studied in conjunction with regulatory responses in the rate of cell proliferation and the cholesterol biosynthetic pathway. We will focus upon the cause and effect relationship between the effects of HDL and HDL subclasses upon cell proliferation and the modulation of HMG CoA reductase activity. As a specific metabolic response, HMG CoA reductase activity will be measured and considered as a reflection of substrate flux into sterols and non-sterol metabolites. The role of various subclasses of HDL in regulating the proliferation of HMG CoA reductase activity of vascular endothelial cells will be analyzed. Increases in enzyme activity will suggest increased rates of synthesis of sterols and/or non-sterol products from mevalonate. These alternatives will be investigated, as will their relationship to the cells' proliferative responses to the lipoproteins. We will also study which components of HDL are necessary in order for it to exert its mitogenic activity, which may occur through more than one mechanism. To this end, the lipid and apoprotein moieties of HDL will be tested and compared for mitogenic activity and metabolic effect on cholesterol efflux and HMG CoA reductase activity. Additionally, reconstituted HDL particles, constructed from various apoproteins and lipid moieties, will be studied.

HDL促进血管内皮细胞增殖的机制 分析内皮细胞。 结合的物理过程， HDL和HDL亚类的内化和降解将被研究 与细胞增殖速率的调节反应结合 和胆固醇生物合成途径。 我们将专注于事业， HDL和HDL亚类对细胞作用的效应关系 增殖和HMG CoA还原酶活性的调节。 作为 将测量特定代谢反应、HMG CoA还原酶活性 并被认为是底物流入甾醇的反映， 非固醇代谢物。 HDL的各种亚类在 调节血管内皮细胞增殖HMG CoA还原酶活性 分析内皮细胞。 酶活性的增加将 表明甾醇和/或非甾醇产物合成速率增加 来自甲羟戊酸 将对这些替代方案进行调查， 与细胞对脂蛋白的增殖反应有关。 我们 我们还将研究HDL的哪些成分是必要的， 发挥其促有丝分裂活性，这可能发生通过一个以上的 机制 为此，HDL的脂质和脱辅基蛋白部分将被 检测并比较促有丝分裂活性和代谢作用， 胆固醇流出和HMG CoA还原酶活性。 此外，本发明还 重组HDL颗粒，由各种载脂蛋白和脂质构成 部分，将进行研究。