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miR-320a 通过促进 ox-LDL 刺激的血管平滑肌细胞迁移和增殖加重动脉粥样硬化。

miR-320a Targeting RGS5 Aggravates Atherosclerosis by Promoting Migration and Proliferation of ox-LDL-Stimulated Vascular Smooth Muscle Cells.

机构信息

Department of Cardiology, Wuhan Puren Hospital, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China; and.

Department of Cardiology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China.

出版信息

J Cardiovasc Pharmacol. 2022 Jul 1;80(1):110-117. doi: 10.1097/FJC.0000000000001286.

DOI:10.1097/FJC.0000000000001286
PMID:35522176
Abstract

MicroRNAs have been implicated in atherosclerosis (AS) progression. Here, we focused on how miR-320a affect AS progression via vascular smooth muscle cells (VSMCs). Oxidized low-density lipoproteins (ox-LDL)-stimulated VSMCs were used as an AS cell model, and qRT-PCR was performed to measure miR-320a and regulators of G protein signaling (RGS5) levels. CCK-8 and wound healing assays were used to detect the viability and migration of VSMCs. Western blotting was used to measure the protein expression levels of PCNA, Bax, and Bcl-2. The interaction of miR-320a and RGS5 was determined by dual luciferase and RNA pull-down assays. MiR-320a was highly expressed, whereas RGS5 showed low levels of expression in the arterial plaque tissues. Silencing of miR-320a blocked cell viability and migration, inhibited expression of the proliferation-specific protein PCNA in ox-LDL-treated VSMCs, promoted Bax protein expression, and inhibited Bcl-2 protein expression. Furthermore, miR-320a was found to exert these effects by inhibiting RGS5 expression. Collectively, miR-320a promoted cell viability, migration, and proliferation while reducing apoptosis of ox-LDL-stimulated VSMCs by inhibiting RGS5.

摘要

微小 RNA 已被牵涉到动脉粥样硬化(AS)的进展中。在这里,我们专注于 miR-320a 如何通过血管平滑肌细胞(VSMCs)影响 AS 的进展。用氧化型低密度脂蛋白(ox-LDL)刺激的 VSMCs 作为 AS 细胞模型,并进行 qRT-PCR 以测量 miR-320a 和 G 蛋白信号调节因子(RGS5)的水平。CCK-8 和划痕愈合试验用于检测 VSMCs 的活力和迁移。Western blot 用于测量增殖特异性蛋白 PCNA、Bax 和 Bcl-2 的蛋白表达水平。通过双荧光素酶和 RNA 下拉测定确定 miR-320a 和 RGS5 的相互作用。动脉斑块组织中 miR-320a 表达上调,而 RGS5 表达下调。沉默 miR-320a 阻断了 ox-LDL 处理的 VSMCs 的细胞活力和迁移,抑制了增殖特异性蛋白 PCNA 的表达,促进了 Bax 蛋白的表达,并抑制了 Bcl-2 蛋白的表达。此外,发现 miR-320a 通过抑制 RGS5 的表达发挥这些作用。总之,miR-320a 通过抑制 RGS5 的表达促进了 ox-LDL 刺激的 VSMCs 的细胞活力、迁移和增殖,同时减少了细胞凋亡。

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