Current perspectives on protective roles of erythropoietin in cardiovascular system: Erythropoietin receptor as a novel therapeutic target

Yutaka Kagaya, Yasuhide Asaumi, Wanting Wang, Morihiko Takeda, Makoto Nakano, Kimio Satoh, Yoshihiro Fukumoto, Hiroaki Shimokawa

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

Erythropoietin (EPO) is a principal regulator that promotes proliferation and terminal differentiation of erythroid progenitor cells. EPO receptors are expressed not only in hematopoietic lineage cells but also in the cardiovascular system. We performed animal experiments using transgene-rescued EPO receptor null mutant mice (EpoR-/-rescued) that express the EPO receptor exclusively in the hematopoietic cells. The results of these experiments suggest that endogenous EPO/EPO receptor system in the heart exerts cardioprotective effects against myocardial injury induced by ischemia followed by reperfusion and pressure-overload induced left ventricular dysfunction. Many animal experiments have shown that the administration of recombinant human EPO also elicits cardioprotective effects against myocardial injury induced by ischemia and reperfusion. In contrast to the promising results of these animal experiments, recent clinical trials failed to demonstrate the reduction in infarct size or improvement of cardiac function by the administration of recombinant human EPO in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. It should be tested in future clinical studies whether a relatively low dose of recombinant human EPO or its derivatives that have no erythropoietic action reduces infarct size and ameliorates cardiac dysfunction in patients with acute myocardial infarction. In this article, we review implications of anemia associated with chronic heart failure, roles of the endogenous EPO/EPO receptor system, and the effects of the administration of erythropoiesis-stimulating agents in pathologic conditions of the heart by focusing on the EPO receptor as a potential candidate of novel therapeutic targets in cardiovascular diseases.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalTohoku Journal of Experimental Medicine
Volume227
Issue number2
DOIs
Publication statusPublished - 2012

Keywords

  • Anemia
  • Erythropoietin
  • Left ventricular hypertrophy
  • Myocardial infarction
  • Ventricular remodeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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