Abstract 13849: Growth Hormone Releasing Hormone (GHRH) Receptor Dependency for Cardioprotective Repair
Background Recently it has been appreciated that the heart harbors GHRH-receptors (GHRHR). Based upon our previous report that potent GHRH agonists are cardioprotective in cardiac injury due to myocardial infarction (MI), we tested the hypothesis that reverse remodeling due to GHRH agonists are clearly receptor dependent by employing a highly selective GHRH-antagonist (MIA-602).
Methods One month post-MI, animals (n=7-10) were randomly assigned to receive: placebo, GHRH-A, rat recombinant GH (rrGH), GHRH-antagonist (MIA-602) or a combination of GHRH-A and MIA-602 for a 4-week period. Cardiac performance was assessed by serial echocardiography and hemodynamic analysis. Morphometric measurements were carried out to determine infarct size and capillary density, and the expression of GHRHR was assessed by immunofluorescence.
Results Over an 8-week period, GHRH-A markedly improved ejection fraction (43±4 vs. 32.7±1.3%, p<0.01). Cardiac benefits were also shown by hemodynamic parameters in the GHRH-A group (see Figure). In addition, MI size was substantially reduced by GHRH-A (29.3±1.4 vs. 40±1.2%, p<0.05) and capillary density was increased (p<0.05 vs. placebo and MIA-602). Importantly, all of these effects were completely abrogated by the GHRH receptor antagonist. The expression of GHRHR was highly detected in both GHRH-A and rrGH groups.
Conclusion Together these findings uncover the importance of the GHRH signaling pathway within the heart. GHRH-A therapy led to substantial improvement in cardiac performance and reduced infarct size after chronic myocardial injury. Importantly, these beneficial effects were blocked by the GHRH-antagonist (MIA-602), confirming a receptor-mediated mechanism. Accordingly, activation of the GHRH receptor signaling pathways represents a novel therapeutic approach to reverse ventricular remodeling post-MI.
- © 2011 by American Heart Association, Inc.