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. 2020;49(5):524-534.
doi: 10.1159/000505571. Epub 2020 Jan 24.

The miR-29b/Matrix Metalloproteinase 2 Axis Regulates Transdifferentiation and Calcification of Vascular Smooth Muscle Cells in a Calcified Environment

Wenhong Jiang  1 , Zhanman Zhang  1 , Han Yang  1 , Qiuning Lin  1 , Xiao Qin  2
Affiliations

The miR-29b/Matrix Metalloproteinase 2 Axis Regulates Transdifferentiation and Calcification of Vascular Smooth Muscle Cells in a Calcified Environment

Wenhong Jiang et al. Blood Purif. 2020.

Abstract

Background: Vascular calcification (VC) is a common pathological lesion that promotes progress and mortality in cardiovascular disease. Vascular smooth muscle cells (VSMCs) acquiring an osteogenic phenotype facilitate VC occurrence and development. We recently reported that miR-29b-3p directly regulates the expression of matrix metalloproteinase 2 (MMP2). Herein, we test whether miR-29b-3p functions in the phenotypic transition and calcification in a calcified environment.

Methods and results: VSMC calcification in vitro was induced with calcification medium containing β-glycerophosphoric acid or high calcium. MiR-29b-3p expression in VSMCs tended to decrease during culturing in calcification medium. MiR-29b-3p overexpression ameliorated VSMC calcification, whereas miR-29b-3p knockdown exacerbated VSMC calcification. Furthermore, ectopic expression of miR-29b-3p inhibited the expression of osteogenic markers and MMP2 (a known target gene of miR-29b-3p). By contrast, miR-29b-3p deficiency facilitated VSMC osteogenesis differentiation and upregulated MMP2 expression.

Conclusion: Our research suggests that miR-29b-3p regulates VSMC calcification and osteogenesis differentiation, at least in part, by targeting MMP2. Regulation of miR-29b-3p expression is therefore a potential therapeutic target for VSMC calcification.

Keywords: Calcification; Matrix metalloproteinase 2; Phenotypic transition; Vascular smooth muscle cell; miR-29b-3p.

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