MicroRNA-27a mediates the Wnt/ß-catenin pathway to affect the myocardial fibrosis in rats with chronic heart failure.

ABSTRACT

OBJECTIVE: To clarify the influence of MicroRNA-27a (miR-27a)-mediated Wnt/ß-catenin pathway on the myocardial fibrosis in rats with chronic heart failure (CHF). METHODS: The CHF rat models were constructed and randomly divided into four groups (Sham, Model, AntagomiR-27a, and NC antagomiR-27a groups). Echocardiography was used to test the cardiac function indexes, HE (haematoxylin-eosin) staining to observe the pathological injury of myocardium, Masson staining to analyze the collagen volume fraction (CVF), and qRT-PCR (quantitative real-time PCR) and Western blotting to detect the expressions of miR-27a and Wnt/ß-catenin pathway-related proteins. Besides, cardiomyocytes were isolated and transfected with miR-27a mimic or miR-27a inhibitor to detect the expressions of Wnt/ß-catenin pathway. RESULTS: The CHF rats were significantly increased in LVESD (left ventricular end systolic diameter) and LVEDD (left ventricular end diastolic diameter), and clearly reduced in FS (fractional shortening) and EF (left ventricular ejection fraction) (all P < 0.05). Moreover, LVWI (left ventricular mass index) and CVF (Collagen Volume Fraction), type I and type III collagen, and the ratio of type I/III collagen, as well as the expression of miR-27a, TGF-ß1 and p-Smad2/3, ß-catenin, p-GSK-3ß and α-SMA were also elevated (all P < 0.05). Additionally, the CHF rats treated with AntagomiR-27a were improved in these indexes, and the expression of miR-27a and Wnt/ß-catenin pathway was significantly inhibited (all P < 0.05). Furthermore, cardiomyocytes transfected with miR-27a inhibitor significantly decreased the levels of miR-27a and Wnt/ß-catenin pathway (all P < 0.05). CONCLUSION: Down-regulation of miR-27a may inhibit the Wnt/ß-catenin pathway to reduce the deposition of myocardial collagen, prevent myocardial fibrosis and improve cardiac function. This article is protected by copyright. All rights reserved.