PHOSPHOLIPID TRANSFER PROTEIN

本提案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。 体外研究提供的证据表明，PLTP在胆固醇稳态的维持、脂质在脂蛋白中的分布中起着核心作用，并且可能在HDL水平和组成的调节中特别重要。 将开发过表达或缺乏PLTP的小鼠模型，并将这些小鼠与动脉粥样硬化易感模型杂交，以确定小鼠中PLTP表达如何影响脂蛋白代谢和动脉粥样硬化。 将在这些小鼠中评价食用普通饲料或高脂肪高胆固醇饲料的脂质、脂蛋白和动脉粥样硬化病变。 将检查胆固醇负荷和细胞增殖抑制对培养细胞表达和分泌PLTP的影响，并确定PLTP是否促进脂质从细胞转运以及通过何种机制促进脂质从细胞转运。 更好地了解PLTP的生理作用可能允许新的治疗方法与早发冠心病相关的脂蛋白紊乱。

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.