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
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]
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