Abstract 18691: Stimulation of Glucagon-Like-Peptide-1 Receptor Through Exendin-4 Preserves Myocardial Performance and Prevents Cardiac Remodeling in Infarcted Myocardium
Background: We have demonstrated that perfusion of GLP-1 improved myocardial functional recovery in acute myocardial ischemic injury. However, it remains unknown whether stimulation of GLP-1 receptor with exendin-4, a selective GLP-1R agonist, could initiate a protective effect in the heart. Objective: We sought to examine whether stimulation of GLP-1R would produce cardioprotection in post chronic myocardial infarction.
Methods: Mouse myocardial infarction (MI) was created by ligation of the left descending artery. After 48 hrs, animals were divided into following groups: 1) MI (n=5): animals that underwent MI and received a daily of intraperitoneal injection (i.p.) saline injection as control; 2) MI + exendin-4 (n=5); infarcted mice received injection of exendin-4 (0.1mg/kg). Two weeks later, ventricular function was measured and cardiac hypertrophy were analyzed.
Results: As compared to control MI hearts, in vivo stimulation of GLP-1R increased the restoration of myocardial functional recovery following MI, which was associated with the prevention of myocardial hypertrophy. GLP-1R stimulation improved the coronary effluent in post-MI hearts. Furthermore, using the in vitro established H9c2 cardiomyoblasts exposed to reactive oxidant species stimulus, we preconditioned H9c2 cardiomyoblasts with exendin-4 at a dose of 100 nmol/L for 1 hr, and they were then subjected to 2 hr of superoxide exposure. In vitro experiments show that the treatment of H9c2 with exendin-4 dramatically decreased the leakage of lactate dehydrogenase (LDH) and increased cell survival, which was also associated with the reduction of apoptosis.
Conclusion: Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection in infarcted hearts and preventing myocardial remodeling.
- © 2013 by American Heart Association, Inc.