Role and mechanism of microRNA-21-5p on myocardial fibrosis aggravating heart failure secondary to myocardial infarction

Abstract

Objective To investigate the role and related mechanism of microRNA-21-5p (miR-21-5p) in heart failure after myocardial infarction (MI). Methods The MI mouse model was established to analyze the expression of miR-21-5p in infarction myocardial zone by quantitative real-time fluorescence PCR. Overexpressed miR-21-5p virus was constructed and conducted in MI mice. Control group was injected with placebo. Immunohistochemical staining was used to identify the degree of myocardial fibrosis, while echocardiography was used to evaluated the heart function after MI. Wound healing assay and CCK-8 assay was used to measure the degree of myocardial fibroblasts by infection with miR-21-5p lentivirus in vitro. Results Compared with the sham group, the expression of miR-21-5p was 1.75-fold higher in MI surgery group (t=8.633, P<0.01). Left ventricular ejection fraction (LVEF) was 31.62%±7.63% and 42.69%±4.47% in miR-21-5p group and control group respectively (t=2.800, P=0.02). Infarct myocardial fibrosis degree was 42.61%±6.73% and 23.23%±4.07% in miR-21-5p group and control group respectively (t=3.470, P=0.01). Smad7 expression significantly decreased in miR-21-5p group and was 0.72-fold compared with control group (t=3.432, P=0.01). Proliferation ability of cardiac fibroblasts was 1.41-fold (t=5.855, P<0.01) and migration ability was 1.41-fold (t=6.658, P<0.01) in miR-21-5p group compared with control group. Conclusions MiR-21-5p may down regulated the expression of Smad7 and promote proliferation and migration of cardiac fibroblasts, further lead to myocardial fibrosis and heart failure after MI. Key words: Myocardial infarction; Heart failure; Cardiac fibrosis; MicroRNA-21-5p; Smad7 protein