MiR-155 regulates macrophage polarization and alleviates myocardial fibrosis through paracrine secretion of transforming growth factor-beta 1 in ischemic heart failure

This study investigated the mechanism underlying miR-155 in ischemic heart failure. The left ventricular ejection fraction (LVEF) in rats was detected by color Doppler echocardiography. After the myocardial tissues were stained with Masson and Sirius red respectively, TGF-βexpression was detected by immunohistochemical staining. Additionally, rat cardiomyocytes were transfected with miR-155 inhibitor, miR-155 mimic, TGF-βagonist or TGF-βinhibitor followed by analysis of levels of miR-155 and TGF-βby real time quantitative PCR. M1 polarization index of lipopolysaccharides (LPS) and M2 type polarization indexes of IL-4, IL-10, and TGF-βwere examined by western blot. Among the three groups of rats, the LVEF of rats in model group was the lowest (p< 0.05) but it was elevated in miR-155 group, whilst the accumulated collagen fibers and hyperplasia in the myocardium were reduced upon miR-155 treatment. Of note, the myocardial tissue of modeled rats had the highest TGF-βlevel, but miR-155 overexpression or inhibitor dramatically decreased TGF-βlevel as well as protein expressions of LPS, IL-4, IL-10, and TGF-β, with the lowest level in miR-155 group. Interestingly, TGF-βagonist treatment resulted in a decrease in LPS while IL-4, IL-10, and TGF-βinhibitor caused opposite outcome. miR-155 can regulate the level of macrophage polarization and paracrine TGF-βand overexpressed miR-155 abrogates the effect of TGF-βon cardiac fibers, alleviating the myocardial ischemic in heart failure. TGF-βcan also affect the biological function of LPS. miR-155 might become a target for the treatment of ischemic heart failure and myocardial fibrosis.