Heal the heart through gut (hormone) ghrelin: a potential player to combat heart failure

Ghrelin, a small peptide hormone (28 aa), secreted mainly by X/A-like cells of gastric mucosa, is also locally produced in cardiomyocytes. Being an orexigenic factor (appetite stimulant), it promotes release of growth hormone (GH) and exerts diverse physiological functions, viz. regulation of energy balance, glucose, and/or fat metabolism for body weight maintenance. Interestingly, administration of exogenous ghrelin significantly improves cardiac functions in CVD patients as well as experimental animal models of heart failure. Ghrelin ameliorates pathophysiological condition of the heart in myocardial infarction, cardiac hypertrophy, fibrosis, cachexia, and ischemia reperfusion injury. This peptide also exerts significant impact at the level of vasculature leading to lowering high blood pressure and reversal of endothelial dysfunction and atherosclerosis. However, the molecular mechanism of actions elucidating the healing effects of ghrelin on the cardiovascular system is still a matter of conjecture. Some experimental data indicate its beneficial effects via complex cellular cross talks between autonomic nervous system and cardiovascular cells, some other suggest more direct receptor-mediated molecular actions via autophagy or ionotropic regulation and interfering with apoptotic and inflammatory pathways of cardiomyocytes and vascular endothelial cells. Here, in this review, we summarise available recent data to encourage more research to find the missing links of unknown ghrelin receptor-mediated pathways as we see ghrelin as a future novel therapy in cardiovascular protection.