晚近研究提示包括miRNA在内的表观遗传机制参与HDL代谢的调控。我们前期研究发现miR-638与HDL代谢异常有关，并提示StarD10为miR-638的潜在靶点。由此推测miR-638可能通过对其靶基因StarD10的表观遗传修饰调节HDL代谢。本课题拟：1、观察miR-638对靶标基因StarD10 mRNA及蛋白表达的影响；2、在细胞水平观察miR-638/StarD10对细胞胆固醇外流、HDL代谢相关基因/蛋白表达及相关细胞信号转导通路的影响；3、模式动物及颈动脉粥样硬化病人中观察miR-638/StarD10对HDL代谢及动脉粥样硬化的影响。拟通过上述研究，确定miR-638对StarD10的调控作用；明确miR-638/StarD10调节HDL代谢的作用及机制。本课题的研究成果，有助于揭示HDL代谢异常的表观遗传学机制，对于寻找HDL代谢异常新的预测指标与治疗靶点有重要意义。

Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Although the role for microRNAs (miRNAs) in regulating multiple physiological processes including apoptosis, cell differentiation, and cancer is well established, the importance of these tiny RNAs in regulating lipid metabolism has only recently been uncovered. Recent advances in the understanding of the regulation of lipid metabolism indicate hat miRNAs play major roles in regulating cholesterol and fatty acid metabolism. These new findings may open new avenues for the treatment of dyslipidemias. We undertook an unbiased genome-wide screen of circulating miRNAs and identified a subset of 20 miRNAs differentially regulated n subjects with low plasma HDL-C levels. Based on the initial data of our study, in the present project, we select miR-638 and its potentially target gene STARD10 for further characterization of its role in the epigenetic regulation in the HDL metabolism.