Exogenous miR-451a prevents MMP-9 upregulation in cardiac hypertrophy

Abstract

Matrix metalloproteinase-9 (MMP-9) degrades extracellular matrix and is increased in several cardiac pathologies. Recently microRNA (miR)-451a has been found to inhibit the expression of MMP-9 in human malignancies. However, its role in regulating MMP-9 in cardiac hypertrophy, has not yet been investigated. We hypothesized that miR-451a would prevent the expression of MMP-9 in cardiac hypertrophy. To test our hypothesis, human induced pluripotent stem cells-derived cardiomyocytes (hiPS-CM) stimulated with endothelin-1 (ET-1) to induce pathological hypertrophy were treated with miR-451a mimic or vehicle control. RT-PCR and MMP-2/MMP-9 activity assay were performed to determine MMP-9 mRNA expression and protein activity, respectively. We found that both mRNA levels of MMP-9 as well as protein activity increased significantly with ET-1 treatment, whereas this increase was prevented by transfecting the cells with miR-451a mimic. Our findings suggest that treating hypertrophic hearts with miR-451a mimic may prevent pathological remodeling, thus serving as a potential novel candidate for targeted treatment of heart failure.