Abstract

Angiogenesis is important for recovery after tissue damage in myocardial ischemia/reperfusion, and tri-iodothyronine (T₃) has documented effects on angiogenesis. The angiopoietins 1/2 and tyrosine kinase receptor represent an essential system in angiogenesis controlling endothelial cell survival and vascular maturation. Recently, in a 3-day ischemia/reperfusion rat model, the infusion of a low dose of T₃ improved the post-ischemic recovery of cardiac function.

Adopting this model, our study aimed to investigate the effects of T₃ on the capillary index and the expression of angiogenic genes as the angiopoietins 1/2 and tyrosine kinase receptor system, in the thoracic aorta and in the left ventricle. In the thoracic aorta, T₃ infusion significantly improved the angiogenic sprouting and angiopoietin 2 expression. Instead, Sham-T₃ group did not show any significant increment of capillary density and angiopoietin 2 expression. In the area at risk (AAR) of the left ventricle, T₃ infusion did not increase capillary density but restored levels of angiopoietin 1, which were reduced in I/R group. Angiopoietin 2 levels were similar to Sham group and unchanged by T₃ administration. In the remote zone, T₃ induced a significant increment of both angiopoietin 1/2. In conclusion, T₃ infusion induced a different response of angiopoietin 1/2 between the ventricle (the AAR and the remote zone) and the thoracic aorta, probably reflecting the different action of angiopoietin 1/2 in cardiomyocytes and endothelial cells. Overall, these data suggest a new aspect of T₃-mediated cardioprotection through angiogenesis.