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

نویسندگان

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

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 (EpoR-/-(rescued)) 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 EpoR-/-(rescued) mice compared with wild-type mice, although the fibrotic area was comparably increased after TAC in the 2 genotypes. In the EpoR-/-(rescued) 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 EpoR-/-(rescued) mice. Vascular endothelial growth factor protein expression and capillary density in left ventricular myocardium were significantly decreased in EpoR-/-(rescued) 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.

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عنوان ژورنال:
  • Circulation

دوره 115 15  شماره 

صفحات  -

تاریخ انتشار 2007