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

Abstract

Abstract. 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.

MiR-21 protected against diabetic cardiomyopathy induced diastolic dysfunction by targeting gelsolin

“…MiR-21 is crucial in a number of biological functions and diseases, including development, cancer, cardiovascular diseases and inflammation [60]. In previous study, we found that miR-21 had a positive function in mitochondrial translation, which was sufficient to reduce blood pressure and alleviate cardiac hypertrophy in spontaneous hypertension rats [39].…”

The next generation of therapeutics for chronic kidney disease

“…Mouse model studies have reported a protective role for miR21 antagonism in heart fibrosis development (Figure 4) 203204 . Moreover, small molecule antagonism of miR21 205 has shown a marked protective effect in several mouse fibrosis models 168 .…”

microRNAs in cardiovascular disease – clinical application

“…Nevertheless, the quantification of miR-208b and miR-499 in myocarditis can potentially be used to determine the severity of the disease [91,127]. Pointing into the same direction are findings that describe miR-21 as an indicator for the transition of chronic myocarditis into dilated cardiomyopathy [128]. These results allow for a disease monitoring in known myocarditis -again only results from cellular analyses of cardiac tissue were reported.…”