REGULATION OF CHOLESTEROL IN VASCULAR ENDOTHELIUM

高密度脂蛋白促进血管增殖的机制 将对内皮细胞进行分析。捆绑的物理过程， 将研究高密度脂蛋白和高密度脂蛋白亚类的内化和降级 结合细胞增殖率的调节反应 和胆固醇的生物合成途径。我们将专注于这一事业，并 高密度脂蛋白与高密度脂蛋白亚类对细胞作用的关系 增殖和HMG辅酶A还原酶活性的调节。作为一名 将测量特定代谢反应、HMG CoA还原酶活性 被认为是底物流入甾醇的反映 非甾醇代谢物。高密度脂蛋白各亚类在细胞周期中的作用 调节血管HMG CoA还原酶活性的增殖 将对内皮细胞进行分析。酶活性的增加将 建议增加甾醇和/或非甾醇产品的合成速度 甲氧戊酸。这些替代方案将被调查，他们的 与细胞对脂蛋白的增殖反应的关系。我们 我还将研究高密度脂蛋白的哪些组成部分是必要的，以便它 发挥其促有丝分裂活性，这可能通过不止一个 机制。为此，高密度脂蛋白的脂质和载脂蛋白部分将 有丝分裂活性和代谢效应的测试和比较 胆固醇外流和HMG辅酶A还原酶活性。另外， 重组的高密度脂蛋白颗粒，由各种载脂蛋白和脂质组成 部分，将被研究。

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.