IL-6 knockout ameliorates myocardial remodeling after myocardial infarction by regulating activation of M2 macrophages and fibroblast cells.

Abstract

To investigate the effects of interleukin-6 (IL-6) gene knockout on myocardial remodeling after myocardial infarction (MI) in mice and the potential mechanism, to provide certain references for the prevention and treatment of MI in clinic. A total of 40 male C57 mice were divided into two groups, namely Sham group (n=20) and MI group (n=20), using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into the MI + IL-6 KO group. The MI model was established by means of ligating the left anterior descending coronary artery of the mice. 28 d later, the survival status of the three groups of mice was recorded. In addition, the cardiac functions of each group of mice, including two-dimensional echocardiography, ejection fraction (EF%) and fractional shortening (FS%), were measured. The cross-sectional area and pathological change of the myocardial cells in cardiac tissues of each group of mice were detected via hematoxylin and eosin (H&E) staining. Immunohistochemistry was applied to determine the expression of tumor necrosis factor-alpha (TNF-α) in each group of mouse cardiac tissues. Moreover, immunofluorescent staining was utilized to measure the content of M2 macrophages in each group of mouse cardiac tissues. The 28-d survival rate of the mice with IL-6 gene knockout was remarkably higher than that of the wild-type mice (p<0.05). Furthermore, the cardiac functions of the mice in the MI + IL-6 KO group were superior to those in the MI group, with markedly improved FS% and EF% (p<0.05). According to the H&E staining results, the cross-sectional areas of the heart and myocardial cells were decreased notably in MI + IL-6 KO group compared with those in the MI group (p<0.05). The immunohistochemical staining results showed that IL-6 knockout could lower the MI-induced high expression of TNF-α (p<0.05), and Masson's trichrome staining indicated that IL-6 knockout could also repress the degree of cardiac fibrosis. Moreover, it was discovered through immunofluorescent staining that the mice in the MI + IL-6 KO group had markedly elevated content of M2 macrophages in cardiac tissues than those in the MI group (p<0.05). Inhibiting IL-6 gene expression can prominently ameliorate the MI-induced myocardial remodeling, whose mechanism is possibly associated with the activation of M2 macrophages and reduced collagen production in fibroblast cells.