Thymosin beta 4 treatment improves left ventricular function after myocardial infarction and is related to Up-regulation of chitinase 3-like-1 in mice

Background: Thymosin beta 4 is a promising agent in preclinical regenerative and cardioprotection research. After myocardial injury it improves cell survival, reduces inflammation and activates epicardial progenitor cells. The peptide is also involved in cardiac purinergic signaling. Methods: We investigated the peptide’s therapeutic potential in a mouse model for myocardial infarction and performed microarray analysis in the early post-infarction period in order to identify new pathways for cardioprotection and also studied its influence on soluble purinergic enzyme activity. In this study 69 mice underwent ligation of the left anterior descending coronary artery. Thymosin beta 4 or vehicle was injected either intraperitoneally or intramyocardially and the mice were followed for 2, 5, 7 or 28 days. Echocardiography was performed 2 and 28 days after infarction. Biochemical analyses were performed to measure apoptosis, cardiomyocyte hypertrophy and inflammation. Results: Treatment improved left ventricular function and reduced cardiac remodeling. The rate of apoptosis and amount of cardiac inflammatory cells were similar between groups. Microarray data showed a significant up-regulation of chitinase 3-like-1 and this was verified by quantitative RT-PCR. The activity of CD73 increased gradually during the first week after infarction and was significantly higher in treated animals compared to controls. Conclusions: Thymosin beta 4 treatment had mild preventive effect on left ventricle remodeling after myocardial infarction. Treated animals showed higher levels of CD73 activity and chitinase 3-like-1, which are novel molecules possibly related to thymosin beta 4 mediated cardioprotection.