PHOSPHOLIPID TRANSFER PROTEIN

这项建议的总体目标是确定血浆磷脂转移蛋白(PLTP)在脂蛋白代谢和动脉粥样硬化中的作用。体外研究已经证明，PLTP在维持胆固醇稳态、脂类在脂蛋白中的分布方面发挥着核心作用，并且可能在调节高密度脂蛋白的水平和组成方面发挥着特别重要的作用。将建立PLTP过表达或缺失的小鼠模型，并与动脉粥样硬化易感模型杂交，以确定PLTP在小鼠体内的表达如何影响脂蛋白代谢和动脉粥样硬化。这些小鼠的血脂、脂蛋白和动脉粥样硬化病变将在饮食或高脂高胆固醇饮食中进行评估。将检测胆固醇负荷和抑制细胞增殖对培养细胞PLTP表达和分泌的影响，并将确定PLTP是否以及通过什么机制促进细胞的脂质运输。更好地了解PLTP的生理作用可能会为治疗与过早冠状动脉疾病相关的脂蛋白紊乱提供新的治疗方法。

The overall goal of this proposal is to determine the role of the plasma phospholipid transfer protein (PLTP) in lipoprotein metabolism and atherosclerosis. In vitro studies have provided evidence that PLTP plays a central role in the maintenance of cholesterol homeostasis, the distribution of lipids among lipoproteins, and is likely to be particularly important in the regulation of HDL levels and composition. Mice models will be developed that either over express or lack PLTP and these mice will be cross bred with atherosclerosis susceptible models in order to determine how PLTP expression in the mouse influences lipoprotein metabolism and atherosclerosis. Lipids, lipoproteins, and atherosclerotic lesions will be evaluated in these mice on either a chow diet or a high fat high cholesterol diet. The effect of cholesterol loading and inhibition of cellular proliferation on expression and secretion of PLTP by cultured cells will be examined and it will be determined if and by what mechanisms PLTP promotes lipid transport from cells. A better understanding of the physiological role of PLTP may permit new therapeutic approaches to lipoprotein disorders associated with premature coronary disease.