Thymosin β4 Protects against Cardiac Damage and Subsequent Cardiac Fibrosis in Mice with Myocardial Infarction

Background. Inflammation is a critical factor in the development and progression of myocardial infarction and cardiac fibrosis. Thymosin beta 4 (T beta 4) alleviates the disease process via protective antioxidant and anti-inflammatory mechanisms. Although T beta 4 has been shown to have a protective effect in myocardial infarction, its impact on cardiac fibrosis has not been well reported. In this study, we evaluated the influence of exogenous T beta 4 on myocardial infarction and cardiac fibrosis and explored the possible underlying mechanism. Methods. Real-time quantitative reverse-transcription PCR (qRT-PCR), immunohistochemistry (IHC), and Western blot were used to analyze T beta 4 expression in acute myocardial infarction (AMI) cardiac tissues. The effects of intraperitoneal adeno-associated virus-T beta 4 (AAV-T beta 4) on ligation-induced AMI in mice were studied using cardiac function parameters, and RT-PCR, Western blot, HE staining, Masson staining, and IHC were used to assess the degree of myocardial fibrosis. The effects of T beta 4 were confirmed in vitro using mouse cardiac myocytes and myofibroblasts. Results. T beta 4 was shown to be significantly elevated in mice AMI cardiac tissues. In mice, AAV-T beta 4 induced exogenous expression of T beta 4 significantly reduced oxidative damage, inflammation, cardiac dysfunction, and fibrosis. H2O2 inhibited mitophagy and increased inflammation in mouse cardiac myocytes via oxidative stress, and T beta 4 substantially reduced mitophagy inhibition and inflammasome activation in myocytes caused by H2O2. Furthermore, T beta 4 decreased cardiac myofibroblast growth and reduced TGF-beta 1-induced activation. Conclusions. AAV-T beta 4 induced expression of T beta 4 reduced inflammation, heart damage, and eventual fibrosis in vivo. T beta 4 helped to reduce oxidative stress, promote mitophagy, and alleviate inflammation and fibrosis. Exogenous supplementation of T beta 4 might be a promising therapeutic agent for treating myocardial infarction as well as cardiac fibrosis.