Abstract
Heart failure creates a leading public health burden worldwide and cardiac fibrosis is a hallmark of pathological cardiac remodeling which was found in HF patients. In this study, we detected the expression of 9 candidate miRNAs in the plasma exosome samples from 31 HF patients, and found the level of miR-21, miR-425 and miR-744 was altered. The downregulation of miR-425 and miR-744 was also found in angiotensin II treated cardiac fibroblasts. Through functional study, we identified that the reduction of miR-425 and miR-744 relates to overexpression of collagen 1 and α-SMA, which result in fibrogenesis of cardiac fibroblasts. Conversely, overexpression of miR-425 or miR-744 in cultured cardiac fibroblasts significantly abrogates angiotensin induced collagen formation and fibrogenesis. Finally, we confirmed that TGFβ1 is a direct target of miR-425 and miR-744 by dual luciferase assay and immunoblotting. Our data demonstrate that miR-425 and miR-744 function as negative regulators of cardiac fibrosis by suppression TGFβ1 expression, and miR-425 and miR-744 level in the plasma exosomes has the potential to be a biomarker to predict cardiac fibrosis and heart failure.