Kaohsiung Journal of Medical Sciences (Nov 2018)

Reduced exosome miR-425 and miR-744 in the plasma represents the progression of fibrosis and heart failure

  • Lu Wang,
  • Jiao Liu,
  • Bin Xu,
  • Yu-Lan Liu,
  • Zhou Liu

Journal volume & issue
Vol. 34, no. 11
pp. 626 – 633

Abstract

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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. Keywords: Heart failure, Fibrosis, miRNA, EGFβ1