Journal
CIRCULATION
Volume 115, Issue 15, Pages 2022-2032Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.106.659037
Keywords
angiogenesis; erythropoietin; heart failure; hypertension; hypertrophy; remodeling
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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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