Abstract 20313: Glucagon-Like-Peptide-1 Receptor Preserves Cardiac Performance and Attenuates Remodeling Through Mkk3 in Infarcted Hearts
Background: We have demonstrated that GLP-1 protects the heart against ischemic injury. However, the physiological mechanism by which GLP-1 receptor (GLP-1R) initiates cardioprotection remains to be determined.
Objectives: This study is sought to elucidate the role of MKK3 in mediating GLP-1R-elicited protection in infarcted hearts.
Methods: Adult wild type (WT), MKK3-/- mice were subjected to myocardial infarction by ligation of the left anterior descending artery. Infarcted mice received a daily intraperitoneal injection of exendin-4, a GLP-1R agonist (0.1mg/kg). Echocardiography was conducted before and 3, 6, 9 weeks after the surgery. Myocardium was collected for evaluation of hypertrophy, apoptosis and angiogenesis.
Results: Exendin-4 preserved cardiac function in WT mice, but functional improvement was not observed in MKK3-/- mice. Exendin-4 treatment induced a reduction of cardiomyocyte size and a decreased collagen deposition in infarcted WT mice only. Elimination of MKK3 abolished the anti-apoptotic effect induced by Exendin-4 in WT mice. Exendin-4 also increased capillary density in WT, but not in MKK3-/- mice. GLP-1R stimulation increased phosphorylation of MKK3, decreased active-caspase 3, poly(ADP-ribose) polymerase (PARP) and annexin V in WT, but not in MKK3-/- mice.
Conclusion: GLP-1R stimulation improves cardiac function, reverses remodeling, and promotes angiogenesis in the infarcted myocardium through MKK3 pathway.
Author Disclosures: J. Du: None. L. Zhang: None. Y. Chen: None. Y. Zhao: None. T.C. Zhao: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.