近年来心脑血管疾病患病人数逐年增多，已成为我国人口死亡的首要原因。动脉粥样硬化（AS）是心脑血管疾病的病理基础，严重威胁人类健康。巨噬细胞是AS形成过程中的主要炎症细胞，维持巨噬细胞脂质代谢平衡可成为防治AS的重要途径。线粒体胆固醇转运蛋白(StAR)是一种胆固醇转运蛋白，本课题组系列研究发现StAR可通过增加氧化固醇维持细胞脂质代谢平衡。最新研究表明细胞自噬参与脂质代谢的调节。本课题预实验发现过表达StAR可升高巨噬细胞中自噬相关基因Atg5、Atg7及LC3-II的表达，抑制FoxO1磷酸化而增加AMPK的磷酸化水平。因此，我们认为StAR可增强巨噬细胞自噬减缓动脉粥样硬化的发生发展，其机制为氧化固醇/FoxO1/AMPK通路。本研究拟在ApoE-/-小鼠、正常及FoxO1或AMPK缺失的巨噬细胞中，研究StAR/氧化固醇与自噬的关系，阐明StAR对动脉粥样硬化保护性作用的分子机制。

In recent years, the prevalence of cardiovascular disease has increased year by year, which has become the leading cause of death in China. Atherosclerosis (AS) is the pathological basis of cardiovascular diseases and puts a heavy burden to the health of human beings. Macrophages are the main inflammatory cells in the formation of AS. To maintain the homeostasis of lipid metabolism in macrophages is one of the important way for prevention and treatment of AS. Mitochondrial cholesterol transporter (StAR) is one of the transporters of cholesterol. Our series of studies found that StAR could maintain the homeostasis of lipid metabolism by increasing regulatory oxysterols. The recent studies indicated that autophagy is involved in the regulation of lipid metabolism. In our preliminary study, overexpression of StAR increased the expression of autophagy-related genes Atg5, Atg7 and LC3-II in macrophages, and StAR overexpression also inhibited the phosphorylation of FoxO1 and increased the phosphorylation level of AMPK. Therefore, we proposed that StAR could retard the development of atherosclerosis by enhancing the autophagy of macrophages,via the oxysterol/FoxO1/AMPK pathway. In this study,we plan to investigate the relationship between StAR/oxysterol and autophagy in ApoE-/- mice, normal macrophages and FoxO1- deficient or AMPK-deficient macrophages, and to elucidate the molecular mechanism of the protective effect on atherosclerosis of StAR.