Unacylated Ghrelin Protects Hearts of Mice Subjected to Myocardial Ischemia/Reperfusion

Abstract

ObjectiveGhrelin can be found in the circulation under two different forms: acylated ghrelin (AG) and unacylated ghrelin (UAG). UAG, while being the predominant ghrelin isoform in circulation, is devoid of endocrine activity. Despite its inability to activate the classical ghrelin receptor, some studies have shown that UAG possesses cardiotropic properties. Our aim is to investigate the cardioprotective effects of UAG against myocardial ischemia‐reperfusion (MI/R) injury.MethodsC57BL/6 mice were pretreated twice a day for 14 days with either AG or UAG at 200 nmol/kg/day. Myocardial ischemia was induced by the ligature of left anterior descending coronary artery for 30 min, followed by reperfusion for 6 or 48 h.ResultsInfarct sizes were reduced by 68 and 60% (P<0.001) in AG‐ (n=6) and UAG‐treated mice (n=5), respectively. Unlike the UAG‐treated group, mice treated with AG showed increased fractional uptake rate (Ki) and net (Km) uptake of free fatty acids (FFA), by 46% (P<0.01) and 44% (P<0.05), respectively, using micropositron emission tomography. Plasma FFA concentrations and glycemia, however, were not significantly different between groups.ConclusionOur results show that both AG and UAG are cardioprotective against MI/R, but exert different cardiometabolic effects, with UAG protecting against the early increased FA uptake following reperfusion of ischemic hearts. Our study suggests that UAG could be a promising therapy to reduce myocardial ischemia/reperfusion injury.Supported by the Heart and Stroke Foundation of Quebec and the Canadian Institutes of Health Research.