A beneficial effects of thymosin beta 4 plasmid on suppression of the extension of myocardial scar formation in rat acute myocardial infarction.
Thymosin beta 4 (Tb4) is a peptide that exists in various kinds of biotissues. Recently, a report on its restorative and regenerative actions on the myocardium has attracted attention. Several studies have already reported on the myocardial-restorative effect of Tb4 peptide in mice. Based on the consideration that local injection of a Tb4 plasmid construct might increase the effect of Tb4, in this study, I compared the effect of locally administered Tb4 plasmid with that of Tb4 peptide. A rat heterotopic abdominal heart transplantation model (Ono-Lindsey method) was employed. At one week after the transplantation, when the transplanted heart in the model rats became stable, both the left anterior descending (LAD) and circumflex (CX) branches of the left coronary artery of the transplanted heart were ligated, which led to the development of a large myocardial infarct. The rats were then divided into four groups; Tb4 plasmid (50 μg/50μl) group, the Tb4 peptide (4.0μg/50μl) group, the control PBS injection group, and the sham group. In each group, injection into the myocardium was given at three or four sites in the myocardial infarct area. The myocardial tissues were harvested 4 weeks later, and the myocardial-restorative effect of Tb4 was assessed. The harvested myocardial specimens were evaluated using Masson Trichrome stain, and the myocardial scar volume rate was examined. The myocardium scar volume rate was reduced significantly in both the Tb4 plasmid and Tb4 peptide groups: Tb4 plasmid group (21.7% ± 10.5%; n = 8; p = 0.004 vs. control); Tb4 peptide group (22.7% ± 6.9%; n = 7; p = 0.016 vs. control); control group (39.1% ± 13.8%; n = 7; p = 0.020 vs. sham (n = 6). Significant reduction of the myocardial scar volume rate was observed in both the Tb4 plasmid and Tb4 peptide groups. There was no significant difference between the two groups in terms of the degree of reduction of the myocardial scar volume. (Accepted on August 26, 2009)
