Effects of MiR-21 on the proliferation and migration of vascular smooth muscle cells in rats with atherosclerosis via the Akt/ERK signaling pathway

P. Sun, L.-N. Tang, G.-Z. Li, Z.-L. Xu, Q.-H. Xu, M. Wang, L. Li

Department of Cadre Health Protection, Liaocheng People’s Hospital, Liaocheng, China. 75106595@qq.com

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• Cardiology

OBJECTIVE: To explore the effects and mechanism of action of micro ribonucleic acid (miR)-21 on the proliferation and migration of vascular smooth muscle (VSM) in atherosclerosis (AS).

MATERIALS AND METHODS: The rats were fed with a high-fat diet, and the oil red staining was adopted to compare AS between Sprague Dawley (SD) rats and miR-21 knockdown rats. At the in-vitro level, primary rat VSM cells (VSMCs) were selected and divided into miR-NC blank control group [miR-normal control (NC) group] and miR-21 overexpression group (miR-21 group) for relevant experimental detection. Wound healing assay and transwell assay were used to detect the effects of miR-21 on the proliferation and migration of VSMCs. Westernn blotting was applied to examine the changes in the levels of Cyclin D, a cell cycle-related protein, and the key factors of the Akt/ERK signaling pathway, such as phosphorylated-Akt (p-AKT), AKT, p-ERK1/2, and ERK1/2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell activity assay kit was applied to determine the effects of miR-21 on the proliferation of VSMCs through regulating the Akt/ERK signaling pathway after the ERK signaling pathway inhibitor PD98059 and AKT inhibitor MK-2206 were given.

RESULTS: Compared with that in miR-NC group, the level of AS in miR-21 knockdown rats were decreased significantly (p < 0.05). In the cell-level experiment, the overexpression of miR-21 promoted abnormal proliferation of VSMCs and activated the Akt/ERK signaling pathway (p < 0.05). MTT assay results revealed that inhibiting the Akt/ERK pathway could reverse the effects of miR-21 promoting proliferation and migration.

CONCLUSIONS: MiR-21 promotes the proliferation and migration of VSMCs by activating the Akt/ERK pathway and aggravates AS. Knocking down miR-21 or inhibiting the Akt/ERK pathway can suppress the activation of VSMCs.

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