title: Epo deficiency alters cardiac adaptation to chronic hypoxia.
abstract: The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAg(h)) and wild-type (WT) mice. Left (LV) and right ventricular functions were assessed by echocardiography and hemodynamics. HIF-1α, VEGF and Epo pathways were explored through RT-PCR, ELISA, Western blot and immunocytochemistry. Epo gene and protein were expressed in cardiomyocytes of WT mice in normoxia and hypoxia. Increase in blood hemoglobin, angiogenesis and functional cardiac adaptation occurred in CHx in WT mice, allowing a normal oxygen delivery (O2T). Epo deficiency induced LV hypertrophy, increased cardiac output (CO) and angiogenesis, but O2T remained lower than in WT mice. In CHx Epo-TAg(h) mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAg(h) mice could not adapt to CHx despite activation of cardioprotective pathways (increased P-STAT-5/STAT-5). HIF/Epo pathway is activated in the heart of WT mice in hypoxia. Chronic hypoxia induced cardiac adaptive responses that were altered with Epo deficiency, failing to maintain oxygen delivery to tissues.
authors: Université Paris 13, Sorbonne Paris Cité, EA2363 Réponses cellulaires et fonctionnelles à l'hypoxie, 93017 Bobigny, France. rajaelhasnaoui@hotmail.com
authors: Raja
authors: R
authors: El Hasnaoui-Saadani
authors: Dominique
authors: D
authors: Marchant
authors: Aurélien
authors: A
authors: Pichon
authors: Brigitte
authors: B
authors: Escoubet
authors: Mylène
authors: M
authors: Pezet
authors: Denise
authors: D
authors: Hilfiker-Kleiner
authors: Melanie
authors: M
authors: Hoch
authors: Isabelle
authors: I
authors: Pham
authors: Patricia
authors: P
authors: Quidu
authors: Nicolas
authors: N
authors: Voituron
authors: Clément
authors: C
authors: Journé
authors: Jean-Paul
authors: JP
authors: Richalet
authors: Fabrice
authors: F
authors: Favret
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D004195:Disease Models, Animal; D004452:Echocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000378:metabolism*; D006321:Heart / Q000502:physiology; D006439:Hemodynamics; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D004921:Erythropoietin