Abstract 16577: Cardioprotective Effect of Growth Hormone Releasing Hormone in Mouse Model of Heart Failure With Preserved Ejection Fraction
Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired relaxation, ventricular stiffening and fibrosis. We previously showed that activation of GHRH signaling axis within the heart had favorable phenotypic effects, particularly improving cardiac function and reducing myocardial fibrosis in murine model of ischemic injury.
Hypothesis: We hypothesized that activation of GHRH receptor signaling can reduce fibrosis and improve diastolic function in a mouse model of HFpEF.
Methods: C57BL6N mice were implanted with a mini-osmotic pump to deliver angiotensin-II (Ang-II: 0.8 mg/kg/day) for 4 weeks and randomly assigned to receive daily injections of GHRH agonist (MR-356: 200 μg/kg) or vehicle. Cardiac performance was assessed by Doppler echocardiography and hemodynamic analysis.
Results: Chronic administration of Ang-II resulted in increased end-diastolic pressure (EDP) with no changes in EF or end-systolic pressure (ESP) in comparison to control mice. Isovolumetric relaxation time (IVRT) and end-diastolic pressure-volume relationship (EDPVR) were markedly increased in the Ang-II group consistent with increased ventricular stiffness and poor myocardial relaxation (Fig 1). MR-356 treatment reset diastolic functional parameters to normal levels (Table 1).
Conclusions: Our findings demonstrate that chronic administration of Ang-II mediates structural and functional changes that mimic HFpEF. Importantly, MR-356 treatment reduces Ang-II-induced elevation of EDP, EDPVR and IVRT; thus preventing HFpEF-like effects, suggesting that administration of MR-356 represents a potential new therapeutic approach for HFpEF.
Author Disclosures: R.M. Kanashiro Takeuchi: None. L.M. Takeuchi: None. C.C. Yuan: None. R.A. Dulce: None. D. Hardin: None. M. Zuttion: None. W. Balkan: None. R.Z. Cai: None. A.V. Schally: None. J.M. Hare: Consultant/Advisory Board; Modest; Vestion Inc.. Consultant/Advisory Board; Significant; significant.
- © 2016 by American Heart Association, Inc.