Open AccessReduced exosome miR‐425 and miR‐744 in the plasma represents the progression of fibrosis and heart failure
Author(s) -
Wang Lu,
Liu Jiao,
Xu Bin,
Liu YuLan,
Liu Zhou
Publication year - 2018
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2018.05.008
Subject(s) - medicine , microvesicles , downregulation and upregulation , fibrosis , microrna , cardiac fibrosis , heart failure , angiotensin ii , exosome , biomarker , cancer research , cardiac function curve , myocardial fibrosis , pathological , gene , biology , blood pressure , biochemistry
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.