Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice

Yasuhide Asaumi, Yutaka Kagaya, Morihiko Takeda, Nobuhiro Yamaguchi, Hiroko Tada, Kenta Ito, Jun Ohta, Takashi Shiroto, Kunio Shirato, Naoko Minegishi, Hiroaki Shimokawa

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

BACKGROUND - Erythropoietin (Epo) receptors (EpoRs) are expressed in the heart. We have recently demonstrated that the endogenous Epo-EpoR system plays an important protective role in myocardial ischemia in mice and humans. In the present study, we tested our hypothesis that the endogenous Epo-EpoR system in nonhematopoietic cells also plays a protective role against pressure overload-induced cardiac dysfunction in vivo. METHODS AND RESULTS - Transgene-rescued EpoR-null mutant mice (EpoRrescued) that express EpoR exclusively in the hematopoietic cells were subjected to transverse aortic constriction (TAC). At 1 week after TAC, left ventricular weight and lung weight were significantly increased in EpoRrescued mice compared with wild-type mice, although the fibrotic area was comparably increased after TAC in the 2 genotypes. In the EpoRrescued mice with TAC, left ventricular end-diastolic diameter was significantly increased, left ventricular fractional shortening was significantly decreased, and survival rate was significantly decreased compared with wild-type mice with TAC. Phosphorylation of STAT3 at 5 hours and 1 week after TAC and that of p38 at 5 hours after TAC were significantly increased in wild-type mice but not in EpoRrescued mice. Vascular endothelial growth factor protein expression and capillary density in left ventricular myocardium were significantly decreased in EpoRrescued mice with TAC compared with wild-type mice with TAC. CONCLUSIONS - These results suggest that the endogenous Epo-EpoR system in the nonhematopoietic cells plays an important protective role against pressure overload-induced cardiac dysfunction in vivo.

Original languageEnglish
Pages (from-to)2022-2032
Number of pages11
JournalCirculation
Volume115
Issue number15
DOIs
Publication statusPublished - 2007 Apr

Keywords

  • Angiogenesis
  • Erythropoietin
  • Heart failure
  • Hypertension
  • Hypertrophy
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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