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

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.