title: Protective role of endogenous erythropoietin system in nonhematopoietic cells against pressure overload-induced left ventricular dysfunction in mice.
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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai 980-8574, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Asaumi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kagaya
authors.forename: Morihiko
authors.initials: M
authors.lastname: Takeda
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tada
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Ohta
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroto
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
authors.forename: Naoko
authors.initials: N
authors.lastname: Minegishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001794:Blood Pressure; D015152:Blotting, Northern; D004452:Echocardiography; D004921:Erythropoietin / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006339:Heart Rate; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009929:Organ Size; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000503:physiopathology*
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin