动脉粥样硬化(As)严重危害人类健康。近来发现剪切应力诱导内皮-间质转化(EndoMT)且在As进程中起着重要作用，但其调控机制不清楚。本项目前期研究发现As斑块内DNA羟甲基化酶TET2表达明显下调，TET2过表达抑制EndoMT以及高脂饮食apoE-/-小鼠As病变；TET2为切应力敏感蛋白，紊流剪切应力下血管内皮细胞(VEC)TET2表达下调。综合文献，我们推测：TET2负性调控“剪切应力-EndoMT”。为证实该假说，本课题将采用颈总动脉局部结扎apoE-/-小鼠模型及平行平板流动腔系统，探讨TET2对“剪切应力-EndoMT”的影响；再基于基因芯片及生物信息学预测的结果，从“miR-320-SOX4-Wnt/β-Catenin”通路探讨TET2调控“剪切应力-EndoMT”的分子机制。本研究的完成将从新的角度阐明EndoMT剪切应力调控机制，为As有效防治提供新策略和新靶点。

Atherosclerosis is a serious risk to human health. Recently, studies showed that endothelial-to-mesenchymal transition (EndoMT) was induced by disturbed flow shear stress, which plays an important role in atherosclerosis progression. However, the detail mechanism is unclear. Our previous studies showed that Ten Eleven Translocation 2 (TET2), a member of DNA hydroxymethylase family, was downregulated in atherosclerotic lesion. In high fat-fed apoE-/- mice, overexpression of TET2 was contributed to inhibited EndoMT and reduced atherosclerotic lesions . Moreover, TET2 is a mechanica sensitivity protein, which was downregulated by disturbed flow shear stress in cultured endothelial cells. Combination with literatures, we hypothesized that TET2 negatively regulated EndoMT induced by disturbed flow shear stress. To test this hypothesis, disturbed flow shear stress apoE-/- mice with partial carotid ligation and parallel plate flow chamber system were used to detect the effect of TET2 on “flow shear stress- EndoMT”. Then, based on the protein Chip and prediction of bioinformatics, “miR-320-SOX4-Wnt/β-Catenin” pathway was detected to explore the regulative mechanism of TET2. The accomplish of this study will explore the mechanical mechanisms of EndoMT, which will further explore the mechanical mechanisms of atherosclerosis and provide new interventional strategies and targets for the prevention and treatment for atherosclerosis.