Abstract 12236: Targeting Growth Hormone Releasing Hormone Receptor as a New Therapeutic Approach to Improve Cardiac Repair After Myocardial Injury
Background: Our previous reports showed that a potent GHRH-agonist (JI-38) is cardioprotective following cardiac injury due to myocardial infarction (MI) in rats. To explore the mechanism by which new agonists of GHRH improve cardiac performance post-MI, we examined the relationship between proliferative capacity of myocyte, infarct size and cardiac performance.
Methods: One month post-MI, rats (n= 6-10) were randomly assigned to receive: 4 weeks of placebo or one of the GHRH-Agonists (GHRH-Ags): JI-38 and new MR-356 or MR-409. Cardiac performance was assessed by serial echocardiography and MI size determined by morphometric measurements. Cardiomyocyte mitotic index and c-kit expression were assessed by immunofluorescence.
Results: At baseline and after MI, echocardiographic parameters of ejection fraction (EF) were similar in all groups. A reduction in EF from to 88±1 to 38±2% (p≤0.05) due to MI was ameliorated in animals treated with GHRH-Ags for 4 weeks (48±1% for each vs. placebo, p≤0.05). MI size was substantially reduced by GHRH-Ags (41±1 vs. 49±2%, p≤0.05). Importantly, these effects were accompanied by an increased number of c-kit+ cells and cellular mitotic division in the myocardium (see table). An inverse correlation was observed between infarct size, and c-kit expression and cardiomyocyte mitotic index.
Conclusion: Activation of GHRH receptor in the heart by GHRH agonists leads to significant recovery of the damaged myocardium and improvements in cardiac function. Reduction of MI size and increase in the number of mitotic cardiomyocytes substantially provide evidence that administration of GHRH agonists enhances myocyte renewal and stimulates cardiac growth after MI providing an effective therapeutic strategy to rescue/repair the infarcted heart.
- © 2013 by American Heart Association, Inc.