老龄化是我国的重要社会问题，心血管疾病是威胁老年人生命健康的“头号杀手”。研究表明动脉粥样硬化的发病率随着年龄增长而逐渐增加，但相关机制还不清楚。血管内皮-间质转化（EndMT）在动脉粥样硬化发生发展中有关键作用，申请人近期研究发现内皮细胞在衰老过程中发生了EndMT，同时SIRT6在EndMT发生过程中明显下调并且抑制SIRT6可促进EndMT的发生。然而，衰老诱发EndMT的调控机制及其对血管内皮结构和功能的影响还未有报道。本课题将在申请人前期工作的基础上深入研究衰老诱发EndMT的发生过程，SIRT6对EndMT的调控作用及机制，并进一步探讨逆转EndMT能否改善内皮功能进而治疗衰老动脉粥样硬化。本课题创新性提出以SIRT6调控血管内皮细胞EndMT为关键点的衰老动脉粥样硬化防治新理念，为老年心血管疾病提供新的治疗靶点和思路，具有重要的理论意义和应用价值。

Aging is becoming a key social problem in China. Cardiovascular diseases are the leading cause of death in the elderly. Studies have shown that the incidence of atherosclerosis increases with age. However, the mechanism of age-related atherosclerosis is still unclear. Endothelial to mesenchymal transition (EndMT) is a crucial process for the development and progress of atherosclerosis. Our preliminary data showed that EndMT occured in aged endothelial cells. Meanwhile, EndMT was associated with downregulation of SIRT6 and depletion of SIRT6 induced EndMT. To our knowledge, the machanism of age-related EndMT has not been previously described and the effect of age-related EndMT on endothelial cells is unclear. Based on our preliminary findings, we will further investigate the occurrence of EndMT in aged endothelial cells, the regulatory mechanism of SIRT6 in EndMT process, and the effect of EndMT reversal on the improvement of endothelial function and repression of age-related atherosclerosis. Our project puts forward the idea that regulating EndMT through SIRT6 is expected to be an effective treatment for age-related atherosclerosis. Our program will provide important clues for the prevention and treatment of age-related cardiovascular diseases.