Myocardial angiogenesis after chronic ghrelin treatment in a rat myocardial infarction model

Ghrelin has a protective role in a rat model of myocardial infarction (MI), but the underlying mechanism is not clear. Here, we investigated the effects of ghrelin treatment on angiogenesis in an experimental rat MI model. Adult male Sprague-Dawley rats were subjected to MI by ligating the anterior descending coronary artery. The rats were then treated with a subcutaneous injection of ghrelin (100 mu g/kg) or saline (control group) for 4 weeks. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. At 28 days after ligation, the ghrelin treatment group showed a higher density of alpha-SMA positive vessels than the saline treatment MI group in myocardial infarct (6 +/- 2.1/mm(2) vs 4 +/- 1.8/mm(2), P<0.05) and pen-infarct zones (25 +/- 9.5/mm(2) vs 15 +/- 5.7/mm(2), P<0.05). RT-PCR and western-blot analyses showed that ghrelin significantly increased vascular endothelial growth factor (VEGF) expression in the pen-infarct zone compared with the control group. Moreover, there was a two-fold increase of Bcl-2 and a 3.5-fold reduction of the Bax protein in the ghrelin-treated MI group compared to the saline treatment MI group. Taken together, ghrelin could induce angiogenesis in rats after MI, the process that may be associated with the enhancement of VEGF and an anti-apoptosis effect. (C) 2012 Elsevier B.V. All rights reserved.