Abstract 10941: Role of an Adipokine Omentin in Myocardial Ischemic Injury
Background: Obesity-linked disorders are closely associated with a severity of ischemic heart disease. Omentin is an adipokine that is downregulated in obese subjects. We have reported that circulating omentin levels are reduced in association with obesity-linked disorders including coronary artery disease. Here, we investigated the impacts of omentin on acute cardiac injury in small and large preclinical animal models of ischemia/reperfusion (I/R) and dissected its molecular mechanism.
Methods and Results: Wild-type mice were subjected to myocardial ischemia followed by reperfusion. An adenoviral vector expressing human omentin (Ad-OMT) or β-galactosidase as a control was intravenously injected into mice at 3 days before surgery. Systemic administration of Ad-OMT to mice led to a reduction of myocardial infarct size and apoptosis following I/R, which were accompanied by increased AMP-activated protein kinase (AMPK) and Akt signaling in the ischemic heart. Systemic delivery of recombinant omentin protein immediately after reperfusion also suppressed myocardial infarct size and apoptosis in response to I/R. In cultured cardiac myocytes, omentin protein suppressed apoptosis in response to hypoxia/reoxygenation, which was reversed by transduction with dominant-negative form of AMPK or Akt. Blockade of AMPK or Akt activity reversed the inhibitory effects of omentin on infarct size and apoptosis in mice in vivo. Furthermore, a bolus intracoronary injection of omentin protein during ischemia reduced infarct size and apoptosis in a pig model of myocardial I/R.
Conclusions: Our data indicate that omentin can prevent myocardial I/R injury by inhibiting apoptosis through modulation of the AMPK- and Akt-dependent pathways, suggesting that omentin represents a therapeutic target for treatment of ischemic heart disease.
- © 2013 by American Heart Association, Inc.