MicroRNA-21 regulation of the progression of viral myocarditis to dilated cardiomyopathy

MicroRNAs (miRNAs) comprise a broad class of small non-coding RNAs that control the expression of complementary target messenger RNAs. The dysregulation of miRNAs by several mechanisms has been described in various disease states, including cardiac disease. Although an etiological link between viral myocarditis (VMC) and idiopathic dilated cardiomyopathy (DCM) has long been recognized, the true extent of this association is uncertain. Previous studies of the two diseases have focused on protein degradation systems. In the present study, miR-21 expression and its potential role in VMC and DCM was investigated. The expression levels of miR-21, its target gene sprouty homolog 1 (SPRY1) and mitogen-activated protein kinase (MAPK) were measured by quantitative polymerase chain reaction. The protein levels of SPRY1 and MAPK were also determined by western blotting. miR-21 levels were significantly increased in cardiac myocytes from VMC and DCM in comparison with control samples. The levels of SPRY1 were decreased and MAPK activity was increased. Using a bioinformatics-based approach, an identical potential binding site was identified in mouse miR-21 and the SPRY 3' untranslated region (3' UTR), suggesting a regulatory role for miR-21. In cultured, miRNA-transfected myocardial cells, the overexpression of miR-21 was associated with a decrease in SPRY1 protein expression and an increased expression of the MAPK protein. These findings revealed that changes in the expression of miRNAs may contribute to the pathogenesis of VMC to DCM and establish the therapeutic efficacy of miRNA targeted intervention in a cardiovascular disease setting.