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

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.

• Authors: 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
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 22 Pg. 1051-1062 (Dec 04 2020) ISSN: 2162-2531 [Print] United States
• PMID: 33294292 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors.