Chronic administration of small nonerythropoietic peptide sequence of erythropoietin effectively ameliorates the progression of postmyocardial infarction-dilated cardiomyopathys

Ismayil Ahmet, Hyun Jin Tae, Michael Brines, Anthony Cerami, Edward G. Lakatta, Mark I. Talan

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The cardioprotective properties of erythropoietin (EPO) in preclinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF). We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, helix B surface peptide (HBSP), that possesses tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in postmyocardial infarction-dilated cardiomyopathy in rats. Starting 2 weeks after permanent left coronary artery ligation, rats received i.p. injections of HBSP (60 mg/kg) or saline two times per week for 10 months. Treatment did not elicit an immune response, and did not affect the hematocrit. Compared with untreated rats, HBSP treatment reduced mortality by 50% (P < 0.05). Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (end-diastolic volume: 41 versus 86%; end-systolic volume: 44 versus 135%; P < 0.05), left ventricle functional deterioration (ejection fraction: 24 versus 263%; P < 0.05), and myocardial infarction (MI) expansion (3 versus 38%; P < 0.05). A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (6365 versus 4064; P < 0.05) and arterioventricular coupling (1.260.2 versus 2.760.7; P < 0.05). Histologic analysis revealed reduced apoptosis (P < 0.05) and fibrosis (P < 0.05), increased cardiomyocyte density (P < 0.05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats. The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post-MI model. There is also a possibility that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct. Thus, HBSP peptide merits consideration for clinical testing.

Original languageEnglish (US)
Pages (from-to)446-456
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume345
Issue number3
DOIs
StatePublished - Jun 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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