Abstract 15424: Ghrelin Attenuates Myocardial Ischemia/Reperfusion Injury via the Extracellular Signal-Regulated Kinase 1/2 and Phosphatidylinositol 3-Kinase/Akt Pathway
Background: Ghrelin is a novel growth hormone-releasing peptide originally isolated from the stomach. Recent study suggests that ghrelin inhibits various cell death through its anti-apoptotic activity in vitro. However, the effect of ghrelin on myocardial ischemia/reperfusion remains unknown in vivo. We hypothesized that ghrelin administration would attenuate myocardial ischemia/reperfusion injury through the extracellular signal-regulated kinase (ERK) 1/2 and Akt serine kinases.
Methods and Results: Male Sprague-Dawley rats were exposed to a 30-minte period of ischemia induced by ligation of the left coronary artery. They were randomized to receive ghrelin (n=20), ghrelin plus U0126 (the ERK 1/2 inhibitor) (n=18), ghrelin plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor) (n=18), or saline (n=20) for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. For detection and quantification of apoptosis, gel electrophoresis of extracted genomic DNA and the terminal dUTP nick-end labelling (TUNEL) method of paraffin sections were performed. We found that endogenous cardiac ghrelin gene expressions were significantly increased in myocardium after ischemia/reperfusion, while plasma ghrelin concentrations were decreased after myocardial ischemia/reperfusion. Intravenous administration of ghrelin significantly reduced myocardial infarct size (32±4 to 22±3 %, P<0.01) and left ventricular end-diastolic pressure (21±3 to 12±3 mmHg, P<0.01). Furthermore, TUNEL-positive myocytes were less frequently observed in the ghrelin-treated group than in the saline-treated group. Although a typical DNA ladder indicating fragmented DNA in cardiomyocytes was also observed in the saline-treated group, it was attenuated in the ghrelin-treated group. These beneficial effects of ghrelin were abolished by the pretreatment with U0126 or wortmannin.
Conclusions: Ghrelin infusion attenuates myocardial ischemia/reperfusion injury. This effect might be attributed to the anti-apoptotic effect of ghrelin via the ERK 1/2 and PI3K/Akt-dependent pathway. These data suggest the potential usefulness of ghrelin as a new cardioprotective agent.
- © 2010 by American Heart Association, Inc.