Ghrelin prevents cardiac cell apoptosis during cardiac remodelling post experimentally induced myocardial infarction in rats via activation of Raf-MEK1/2-ERK1/2 signalling

Context: Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear. Objective: To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway. Materials and methods: Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 mu g/kg) was administered for 21 days, starting one-day post-MI. Results: Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser(338)), phospho-MEK1/2 (Ser(217/221)), phospho-ERK1/2 (Thr(202)/Tyr(204)), and of their downstream target p-BAD (Ser(112)) and inhibited the cleavage of caspase-3. Concomitantly, ghrelin prevented the increases in the levels of fibrotic markers, including alpha-smooth muscle actin (alpha-SMA), metalloproteinase-9 (MPP-9), and type III collagen. Conclusion: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.