血管钙化导致严重心血管事件但防治困难。血管平滑肌细胞向成骨细胞表型分化是其重要细胞学基础。已有临床研究表明多不饱和脂肪酸（PUFAs）可降低血管钙化风险，但n-6/n-3 PUFAs在膳食和机体代谢中的比例失衡增加心血管事件发生风险，其机制不明。课题组前期研究中发现fat-1 (使n-6转化为n-3 PUFAs的酶)转基因可明显抑制小鼠血管平滑肌细胞mTORC1活性，并减少血管钙化发生。而血管平滑肌细胞自噬是血管钙化重要的内源性保护性机制，mTORC1是自噬的主要调节蛋白。据此我们推测：n-6/n-3 PUFAs通过抑制mTORC1信号通路，进而增强血管平滑肌细胞自噬水平，抑制血管钙化形成。本项目拟采用fat-1转基因小鼠、腺病毒等工具，阐明n-6/n-3 PUFAs抑制血管钙化及调控血管平滑肌细胞自噬、细胞表型转化的分子靶点和分子机制，为探寻防治血管钙化新方法提供思路和依据。

Vascular calcification is a major risk factor for cardiovascular morbidity and mortality, and it is prevalent in the patients with diabetes and atherosclerosis. There is no available therapy that could reverse vascular calcification at present. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is the cellular mechanism that mediates vascular calcification. It is reported that polyunsaturated fatty acids (PUFAs) exhibit various protective effects against vascular smooth muscle cell (VSMC) inflammation and proliferation in cardiovascular remodeling. Although the ratio of n-3 PUFA to n-6 PUFAs had recently been recognized as a risk marker of cardiovascular disease, the molecular mechanisms of PUFAs on the calcium release from VSMCs have not been clearly elucidated, and it is necessary to identify the molecular mechanism of PUFAs in the early stage of vascular calcification processes. In the prior research, we had found that endogenously produced n-3 PUFAs can attenuate vascular calcification, mainly as a consequence of keeping VSMCs steadily. In addition, it showed that one critical downstream target protein of mTORC1, p-S6 , significantly reduced in fat-1 transgenic mice . Autophagy, which is mainly regulated by mTORC1 signaling , is considered to play a pivotal role in vascular calcification. According to these results, we hypothesed that n-6/n-3 PUFAs inhibits vascular calcification by promoting autophagy via suppression of the mTORC1 signaling pathway. Here, we investigate whether n-6/n-3 PUFAs attenuates vascular calcification by regulating autophagy in VSMCs in vitro and in vivo and explore the mechanism involved. These questions to be solved will contribute to find a new target for prevention and cure of vascular calcification.