Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, Hunan, 421001, China; School of Nursing, Xiangnan University, Chenzhou, Hunan, 423000, China.
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, University of South China, Hengyang, Hunan, 421001, China.
Biochem Biophys Res Commun. 2021 Mar 19;545:20-26. doi: 10.1016/j.bbrc.2021.01.062. Epub 2021 Jan 31.
Atherosclerotic cardiovascular disease is the major cause of death worldwide. Low shear stress plays key roles on the initiation and progression of atherosclerosis (As). However, its underlying mechanism remains unclear. In this study, the effect of low shear stress on endothelial mesenchymal transformation (EndMT) and its underlying mechanism were explored. Results showed that in cultured human umbilical vein endothelial cells, low shear stress down-regulated the expression of TET2 and promoted EndMT. Loss of TET2 promoted EndMT with the Wnt/β-catenin signaling pathway. The enhancement in EndMT induced by low shear stress was attenuated by TET2 overexpression. In apoE mice subjected to carotid artery local ligation, the EndMT and atherosclerotic lesions induced by low shear stress was attenuated by TET2 overexpression. Taken together, low shear stress promoted EndMT through the down-regulation of TET2, indicating that intervention with EndMT or the up-regulation of TET2 might be an alternative strategy for preventing As.
动脉粥样硬化性心血管疾病是全球主要的死亡原因。低切应力在动脉粥样硬化（As）的发生和发展中起着关键作用。然而，其潜在机制尚不清楚。在这项研究中，探讨了低切应力对血管内皮细胞向间充质转化（EndMT）的影响及其潜在机制。结果表明，在培养的人脐静脉内皮细胞中，低切应力下调了 TET2 的表达，促进了 EndMT。TET2 的缺失促进了 Wnt/β-catenin 信号通路的 EndMT。TET2 的过表达减弱了低切应力诱导的 EndMT。在接受颈动脉局部结扎的载脂蛋白 E 小鼠中，TET2 的过表达减轻了低切应力诱导的 EndMT 和动脉粥样硬化病变。综上所述，低切应力通过下调 TET2 促进 EndMT，表明干预 EndMT 或上调 TET2 可能是预防 As 的一种替代策略。
