Abstract
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. 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. 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. 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.
Highlights
Thymosin beta 4 is a promising agent in preclinical regenerative and cardioprotection research
We wanted to test the effect of Thymosin beta 4 (TB4) in a mouse myocardial infarction (MI) model using standard biochemical methods for assessing cardioprotection and serial echocardiography to determine changes in left ventricular function and remodeling
Since infarct sizes with ligation models vary depending on technical success we wanted to determine the change in these parameters over time and compared early and late functional and structural outcome after MI, which better reflects disease progression
Summary
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 involved in cardiac purinergic signaling. After myocardial infarction (MI) it reduces infarct size and remodeling of the left ventricle (LV) leading to improved cardiac function. We wanted to test the effect of TB4 in a mouse MI model using standard biochemical methods for assessing cardioprotection and serial echocardiography to determine changes in left ventricular function and remodeling. Since infarct sizes with ligation models vary depending on technical success we wanted to determine the change in these parameters over time and compared early and late functional and structural outcome after MI, which better reflects disease progression. In addition we screened plasma samples for possible involvement of soluble purine-converting enzymes in TB4-mediated cardioprotection
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