MicroRNA-22 Inhibits the Apoptosis of Vascular Smooth Muscle Cell by Targeting p38MAPKα in Vascular Remodeling of Aortic Dissection.
MicroRNA-22 Inhibits the Apoptosis of Vascular Smooth Muscle Cell by Targeting p38MAPKα in Vascular Remodeling of Aortic Dissection.
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DOI：
10.1016/j.omtn.2020.08.018
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Jing Z
中科院分区：
文献类型：
--
作者：
Xiao Y;Sun Y;Ma X;Wang C;Zhang L;Wang J;Wang G;Li Z;Tian W;Zhao Z;Jing Q;Zhou J;Jing Z
microRNA 22（miR-22）在多种心血管疾病中被发现在调节多种细胞过程中起作用。然而，miR-22在主动脉夹层（AD）中的调控作用仍不清楚。探讨miR-22在人主动脉中的表达。采用模拟、抑制或小干扰RNA（siRNA）质粒转染血管平滑肌细胞（VSMC），观察miR-22和p38丝裂原活化蛋白激酶α（p38 MAPK α）对VSMC凋亡的影响。此外，建立小鼠AD模型，并进行组织病理学分析以评估miR-22的调节作用。在人AD主动脉中观察到miR-22减少和VSMCs凋亡增加。下调miR-22可增加体外培养的VSMCs凋亡。生物信息学分析显示p38 MAPK α是miR-22的靶点。抑制p38 MAPK α表达可逆转miR-22下调诱导的VSMCs凋亡。AD小鼠模型中miR-22的敲低显著促进AD的发展。我们的数据强调了血管重塑和VSMC功能在AD中的重要性。miR-22可能通过MAPK信号通路调控血管平滑肌细胞凋亡，为AD的治疗提供新的途径。这项研究表明，miR-22可能通过MAPK信号通路调节VSMC的凋亡，代表了主动脉夹层的一种新的治疗方法。该研究为AD的机制和创新的治疗策略提供了新的见解，为小分子治疗提供了新的靶点。
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. This study indicates miR-22 may represent a new therapeutic approach for aortic dissection by regulating the apoptosis of VSMCs through the MAPK signaling pathway. The study provided a novel insight into the mechanism of AD and the innovative therapeutic strategies in the form of new targets for small molecule therapies.
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影响因子：
30.5
作者：
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作者：
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