Abstract 9927: Helix B Surface Peptide, a Small Non-erythropoietic Molecule Based on the Erythropoietin Structure, Effectively Ameliorates the Progression of Chronic Heart Failure in the Rat Post Myocardial Infarction Model
The cardioprotective properties of Erythropoietin (EPO) are well documented in pre-clinical studies. However, due to its erythropoietic and prothrombotic properties, the EPO treatment cannot be used in chronic heart failure (CHF), unless indicated by accompanied anemia. Helix B surface peptide (HBSP), a small peptide synthetized on the basis of EPO molecule (ARA290, Araim Pharmaceutical), does not stimulate erythropoiesis. We have reported similarly strong cardioprotective effects of HBSP and EPO in the rat model of myocardial infarction (MI). In this study, we tested the effect of long-term treatment with HBSP on mortality and cardiac remodeling in post-MI CHF in rats. For the 10 months, starting two weeks after left coronary artery ligation, rats received the i.p. injections of HBSP (60µg/kg; n=33) or saline (n=33) 2 times per week. Compared to saline-treated rats, HBSP treatment significantly reduced mortality (35% vs. 65%; p<0.05). Repeated Echocardiography demonstrated remarkable attenuation of left ventricular (LV) chamber dilatation (EDV: 41% vs. 86%; ESV: 44% vs. 135%; p<0.05), LV functional deterioration (EF: -4% vs. -63%; p<0.05) and MI expansion (3% vs. 38%; p<0.05) in HPSP-treated rats compared to saline-treated rats. Blood hematocrit level measured monthly was not affected by HBSP treatment. An invasive hemodynamic assessment at the end of 10-mo treatment showed better LV systolic function (PRSW: 63±5 vs. 40±4; p<0.05) and Arterio-ventricular coupling (Ea/Ees: 1.2±0.2 vs. 2.7±0.7; p<0.05) in HBSP-treated rats compared to saline-treated rats. Histological analysis revealed less apoptosis (0.6±0.1% vs. 0.9±0.1%; p<0.05), myocardial fibrosis (2.6±0.2% vs. 4.1±0.5%; p<0.05), and myocyte hypertrophy (cell diameter: 31±1µm vs. 37±1µm; p<0.05) in non-infarcted myocardium among HBSP-treated rats compared to saline-treated rats. Results suggest that HBSP could be considered as a safe alternative to EPO for a further clinical testing in the patients with chronic heart failure.
- © 2012 by American Heart Association, Inc.