MiR155-5p Inhibits Cell Migration and Oxidative Stress in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats
MiR155-5p Inhibits Cell Migration and Oxidative Stress in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats
复制标题
MiR155-5p抑制自发性高血压大鼠血管平滑肌细胞迁移和氧化应激
DOI：
10.3390/antiox9030204
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发表时间：
2020-03-01
期刊：
影响因子：
7
通讯作者：
Zhu, Guo-Qing
中科院分区：
文献类型：
--
作者：
Wu, Nan;Ye, Chao;Zhu, Guo-Qing
血管平滑肌细胞(VSMCs)的迁移在高血压和多种血管疾病的血管重建中是必不可少的。我们最近的研究表明，来自正常大鼠血管外膜成纤维细胞的细胞外小泡通过将miR155-5P传递给VSMC而抑制VSMC的增殖。目前尚不清楚miR155-5p是否抑制自发性高血压大鼠(SHR)和血管紧张素II(Ang II)处理的VSMCs的细胞迁移和氧化应激。本研究旨在探讨miR155-5p在VSMC迁移中的作用及其机制。从Wistar-京都大鼠(WKY)和自发性高血压大鼠(SHR)的主动脉中分离出原代VSMCs。采用创面愈合实验和Boyden小室实验评价VSMC的迁移。MiR155-5p模拟抑制剂和miR155-5p抑制剂可促进SHR的VSMC迁移，但对WKY的VSMC迁移无明显影响。MiR155-5p模拟物抑制血管平滑肌细胞血管紧张素转换酶(ACE)基因和蛋白的表达。还可降低自发性高血压大鼠血管平滑肌细胞超氧阴离子生成量、NAD(P)H氧化酶活性、一氧化氮合成酶2、白介素1β(IL-1β)和肿瘤坏死因子α(肿瘤坏死因子α)的表达水平，但对WKY大鼠血管平滑肌细胞无明显影响。MiR155-5p过表达抑制自发性高血压大鼠血管平滑肌细胞迁移和超氧阴离子及IL-1β的产生，但对外源性血管紧张素转换酶II诱导的血管平滑肌细胞迁移及超氧阴离子和IL-1β的产生无影响。这些结果表明miR155-5p通过抑制血管紧张素转换酶表达及其下游血管紧张素转换酶II、超氧阴离子和炎症因子的产生而抑制自发性高血压大鼠VSMC的迁移。但miR155-5p对外源性Ang II诱导的VSMC迁移无影响。
Migration of vascular smooth muscle cells (VSMCs) is essential for vascular reconstruction in hypertension and several vascular diseases. Our recent study showed that extracellular vesicles derived from vascular adventitial fibroblasts of normal rats inhibited VSMC proliferation by delivering miR155-5p to VSMCs. It is unknown whether miR155-5p inhibits cell migration and oxidative stress in VSMCs of spontaneously hypertensive rats (SHR) and in angiotensin II (Ang II)-treated VSMCs. The purpose of this study was to determine the role of miR155-5p in VSMC migration and its underlying mechanisms. Primary VSMCs were isolated from the aortic media of Wistar-Kyoto rats (WKY) and SHR. Wound healing assay and Boyden chamber assay were used to evaluate VSMC migration. A miR155-5p mimic inhibited, and a miR155-5p inhibitor promoted the migration of VSMC of SHR but had no significant effect on the migration of VSMC of WKY. The miR155-5p mimic inhibited angiotensin-converting enzyme (ACE) mRNA and protein expression in VSMCs. It also reduced superoxide anion production, NAD(P)H oxidase (NOX) activity, as well as NOX2, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) expression levels in VSMCs of SHR but not in VSMCs of WKY rats. Overexpression of miR155-5p inhibited VSMC migration and superoxide anion and IL-1β production in VSMCs of SHR but had no impact on exogenous Ang II-induced VSMC migration and on superoxide anion and IL-1β production in WKY rats and SHR. These results indicate that miR155-5p inhibits VSMC migration in SHR by suppressing ACE expression and its downstream production of Ang II, superoxide anion, and inflammatory factors. However, miR155-5p had no effects on exogenous Ang II-induced VSMC migration.