Inhibition of microRNA‑155 ameliorates cardiac fibrosis in the process of angiotensin II‑induced cardiac remodeling.

Abstract

Cardiac fibrosis triggered by pressure overload represents one of the major challenges in the treatment of cardiovascular diseases. MicroRNA (miRNA/miR)-155, a member of the small RNA family, has previously been demonstrated to be associated with cardiac inflammation. However, the effect of miR-155 on cardiac fibrosis induced by angiotensin II (Ang II), particularly in cardiac fibroblasts, requires further investigation. The present study aimed to investigate the effect of miR-155 in Ang II-induced cardiac fibrosis using animal models and cardiac fibroblasts. Animal models were established in male miR-155−/− and wild-type (WT) C57Bl/6J mice (10–12 weeks old) by Ang II infusion using subcutaneously implanted minipumps. After 8 weeks of Ang II infusion, the results demonstrated that the deletion of miR-155 in mice markedly ameliorated ventricular remodeling compared with WT mice, as demonstrated by restricted inflammatory responses, decreased heart size, improved cardiac function and reduced myocardial fibrosis. In vitro, overexpression of miR-155 in cardiac fibroblasts led to significantly increased fibroblast to myofibroblast transformation. However, this effect was abrogated by miR-155 silencing. In conclusion, the results of the present study indicate that genetic loss of miR-155 in mice ameliorates cardiac fibrotic remodeling following pressure overload. Therefore, inhibiting miR-155 may have potential as an adjunct to reduce cardiac inflammation in the treatment of cardiac fibrosis.