REGULATION OF CHOLESTEROL IN VASCULAR ENDOTHELIUM

血管内皮胆固醇的调节

• 批准号: 3337359
• 负责人: DENIS J GOSPODAROWICZ
• 金额: $ 11.8万
• 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 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3337359
• 关键词: HMG coA reductases; affinity chromatography; atherosclerosis; blood lipoprotein transport; cell differentiation; cholesterol; fatty acid biosynthesis; fibroblast growth factor; fluorescence microscopy; human tissue; liposomes; low density lipoprotein; mevalonate; radioimmunoassay; radiotracer; terpenes; tissue /cell culture; ultracentrifugation; vascular smooth muscle; very low density lipoprotein

The effect and mechanisms through which lipoproteins regulate MVA metabolism and act as competence factors for cultured cells will be analyzed using as models normal diploid cells (capillary endothelial cells (CE), vascular smooth muscle cells) and an established cell line (MDCK cells). The ability of very low density lipoproteins (VLDL) which are LDL precursors to support cell shape and proliferation will be determined using cultures exposed or not to compactin. Their effects will be compared to that of HDL. As a specific VLDL and HDL metabolic response, their effect on HMG-CoA reductase will be measured and considered as a reflection of substrate flux into sterols and nonsterol metabolites. We will determine which key nonsterol products resulting from MVA metabolism would be relevant to the control of cell proliferation and cell shape and would explain the ability of lipoproteins to act as competence factors. Our attention will be focused on the synthesis of terpenes which modify specific polypeptides post translationally. The effect of HDL, VLDL and isolated components (phospholipid liposomes, apolipoproteins) on terpene synthesis and their incorporation into polypeptides as well as the effect of b FGF ( a progression factor for CE cells) on such a process will be examined using as models sparse CE cells exposed or not to compactin.

脂蛋白调节的作用和机制 MVA代谢并作为培养细胞的感受态因子 将使用正常二倍体细胞（毛细血管）作为模型进行分析 内皮细胞（CE）、血管平滑肌细胞）和 建立的细胞系（MDCK细胞）。 能力很低 密度脂蛋白（VLDL），其是LDL前体，以支持 将使用培养物测定细胞形状和增殖 暴露于或不暴露于压缩蛋白。 它们的效果将与 HDL的。 作为一种特定的VLDL和HDL代谢反应， 将测量它们对HMG-CoA还原酶的作用， 被认为是底物流入甾醇的反映， 非固醇代谢物。 我们将确定哪些关键的非固醇 MVA代谢产生的产物与 控制细胞增殖和细胞形状，并解释了 脂蛋白作为感受态因子的能力。 我们 注意力将集中在萜烯的合成上， 修饰特异性多肽。 的影响 HDL、VLDL和分离的组分（磷脂脂质体， 载脂蛋白）对萜烯合成的影响以及它们掺入 多肽以及B FGF（进展因子）的作用 对于CE电池）在这样的过程中将被检查使用作为模型 稀疏的CE细胞暴露于或不暴露于压缩蛋白。