MiR-634 inhibits human vascular smooth muscle cell proliferation and migration in hypertension through Wnt4/β-catenin pathway.

Li-Gang Niu ,Na Sun,Lingheng Kong,Yan Xu,Yu-Ming Kang

doi:10.52586/4953

Abstract

MicroRNAs (miRNAs) have been regarded as modulators in vascular pathologies, including hypertension. Dysregulated proliferation and migration of VSMCs (vascular smooth muscle cells) contributes to vascular remodeling during hypertension. miR-634 was reported to be dysregulated in hypertensive patients. The involvement of miR-634 in hypertension and the role of miR-634 on VSMCs proliferation and migration were then evaluated. Firstly, HASMCs (human aortic smooth muscle cells) were incubated with 2 μM angiotensin (Ang) II for 12 hours to establish the cell model of Ang II-induced hypertension. Results showed that Ang II treatment promoted proliferation and migration of HASMCs. Secondly, miR-634 was down-regulated in the hypertensive patients, and reduced in Ang II-induced HASMCs in a time dependent manner. Functional assays revealed that Ang II promoted proliferation and migration of HASMCs were suppressed by miR-634 mimic. Lastly, miR-634 targeted 3' untranslated region (UTR) of Wnt4, and reduced Wnt4 expression in HASMCs. miR-634 inhibited β-catenin nuclear translocation. Over-expression of Wnt4 counteracted the suppressive effects of miR-634 on Ang II-induced proliferation and migration of HASMCs. In conclusion, miR-634 inhibited HASMCs proliferation and migration through inactivation of Wnt4/β-catenin pathway.

Highlights

Hypertension causes cardiovascular diseases and is considered as a world-wide disease [1]
Cotransfection with miR-634 mimic and pcDNA-Wnt4 attenuated the promotive effects of Wnt4 on Ang II-induced HASMCs proliferation (Fig. 4A) and migration (Fig. 4B,C). These results showed that miR-634/Wnt4 axis participated in regulation of Ang II-induced HASMCs proliferation and migration
Data in this study showed that miR-634 increased cytoplasmic distribution of β-catenin, while overexpression of Wnt4 or in vitro Wnt4 treatment reversed the suppressive effect of miR-634 on nuclear distribution of β-catenin, suggesting that Wnt/β-catenin pathway was involved in miR-634-mediated hypertension

Summary

Introduction

Hypertension causes cardiovascular diseases and is considered as a world-wide disease [1]. The etiology of hypertension is complicated with various pathogenic factors. Environmental and genetic factors could lead to increased blood pressure through affecting physiological processes [2], leading to hypertension [3]. Overreaction of renin-angiotensin-aldosterone system, dysfunction of vascular endothelial cells, cardiac hypertrophy and platelet function injury have been widely regarded as pathogenesis of hypertension [4]. Vascular remodeling, associated with dysregulated proliferation and migration of VSMCs, is the central mechanism for hypertension [5]. Inhibition of VSMCs proliferation and migration represents an effective therapeutic strategy for hypertension [6]

Methods

Results

Discussion

Conclusion