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. 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.

journal_name

Circulation

journal_title

Circulation

authors

Asaumi Y,Kagaya Y,Takeda M,Yamaguchi N,Tada H,Ito K,Ohta J,Shiroto T,Shirato K,Minegishi N,Shimokawa H

doi

10.1161/CIRCULATIONAHA.106.659037

subject

Has Abstract

pub_date

2007-04-17 00:00:00

pages

2022-32

issue

15

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.106.659037

journal_volume

115

pub_type

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