MicroRNA-22 Inhibits the Apoptosis of Vascular Smooth Muscle Cell by Targeting p38MAPKα in Vascular Remodeling of Aortic Dissection

MicroRNA-22通过靶向p38MAPKα抑制主动脉夹层血管重塑中血管平滑肌细胞凋亡

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作者:Yu Xiao, Yudong Sun, Xiang Ma, Chen Wang, Lei Zhang, Jiannan Wang, Guokun Wang, Zhenjiang Li, Wen Tian, Zhiqing Zhao, Qing Jing, Jian Zhou, Zaiping Jing

Abstract

MicroRNA 22 (miR-22) was found in diverse cardiovascular diseases to have a role in regulating multiple cellular processes. However, the regulatory role of miR-22 in aortic dissection (AD) was still unclear. The miR-22 expression in human aorta was explored. A series of mimic, inhibitor, or small interfering RNA (siRNA) plasmids were delivered into vascular smooth muscle cells (VSMCs) to explore the effects of miR-22 and p38 mitogen-activated protein kinase α (p38MAPKα) in controlling VSMC apoptosis in vitro. In addition, a mouse AD model was established, and histopathologic analyses were performed to evaluate the regulatory effects of miR-22. Reduced miR-22 and increased apoptosis of VSMCs was seen in human AD aorta. Downregulation of miR-22 increased the apoptosis of VSMCs in vitro. Bioinformatics analyses revealed that p38MAPKα was a target of miR-22. Inhibiting p38MAPKα expression could reverse the apoptosis of VSMCs induced by miR-22 downregulation. Knockdown of miR-22 in the AD mouse model significantly promoted the development of AD. Our data underscore the importance of vascular remodeling and VSMC function in AD. miR-22 may represent a new therapeutic approach for AD by regulating the apoptosis of VSMCs through the MAPK signaling pathway.

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