Epo deficiency alters cardiac adaptation to chronic hypoxia

Raja El Hasnaoui-Saadani, Dominique Marchant, Aurélien Pichon, Brigitte Escoubet, Mylène Pezet, Denise Hilfiker-Kleiner, Melanie Hoch, Isabelle Pham, Patricia Quidu, Nicolas Voituron, Clément Journé, Jean Paul Richalet, Fabrice Favret

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAgh) 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-TAgh mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAgh 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.

Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalRespiratory Physiology and Neurobiology
Volume186
Issue number2
DOIs
Publication statusPublished - 1 Apr 2013

Fingerprint

Erythropoietin
Cardiac Output
Hypertrophy
Oxygen
Right Ventricular Function
Hypoxia
Left Ventricular Function
Cardiac Myocytes
Vascular Endothelial Growth Factor A
Echocardiography
Hemoglobins
Hemodynamics
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Polymerase Chain Reaction
Proteins

Keywords

  • Anemia
  • Erythropoietin
  • Hypoxia
  • Myocardial contractility
  • Myocardial vascularisation

Cite this

El Hasnaoui-Saadani, R., Marchant, D., Pichon, A., Escoubet, B., Pezet, M., Hilfiker-Kleiner, D., ... Favret, F. (2013). Epo deficiency alters cardiac adaptation to chronic hypoxia. Respiratory Physiology and Neurobiology, 186(2), 146-154. https://doi.org/10.1016/j.resp.2013.01.003
El Hasnaoui-Saadani, Raja ; Marchant, Dominique ; Pichon, Aurélien ; Escoubet, Brigitte ; Pezet, Mylène ; Hilfiker-Kleiner, Denise ; Hoch, Melanie ; Pham, Isabelle ; Quidu, Patricia ; Voituron, Nicolas ; Journé, Clément ; Richalet, Jean Paul ; Favret, Fabrice. / Epo deficiency alters cardiac adaptation to chronic hypoxia. In: Respiratory Physiology and Neurobiology. 2013 ; Vol. 186, No. 2. pp. 146-154.
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El Hasnaoui-Saadani, R, Marchant, D, Pichon, A, Escoubet, B, Pezet, M, Hilfiker-Kleiner, D, Hoch, M, Pham, I, Quidu, P, Voituron, N, Journé, C, Richalet, JP & Favret, F 2013, 'Epo deficiency alters cardiac adaptation to chronic hypoxia', Respiratory Physiology and Neurobiology, vol. 186, no. 2, pp. 146-154. https://doi.org/10.1016/j.resp.2013.01.003

Epo deficiency alters cardiac adaptation to chronic hypoxia. / El Hasnaoui-Saadani, Raja; Marchant, Dominique; Pichon, Aurélien; Escoubet, Brigitte; Pezet, Mylène; Hilfiker-Kleiner, Denise; Hoch, Melanie; Pham, Isabelle; Quidu, Patricia; Voituron, Nicolas; Journé, Clément; Richalet, Jean Paul; Favret, Fabrice.

In: Respiratory Physiology and Neurobiology, Vol. 186, No. 2, 01.04.2013, p. 146-154.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Epo deficiency alters cardiac adaptation to chronic hypoxia

AU - El Hasnaoui-Saadani, Raja

AU - Marchant, Dominique

AU - Pichon, Aurélien

AU - Escoubet, Brigitte

AU - Pezet, Mylène

AU - Hilfiker-Kleiner, Denise

AU - Hoch, Melanie

AU - Pham, Isabelle

AU - Quidu, Patricia

AU - Voituron, Nicolas

AU - Journé, Clément

AU - Richalet, Jean Paul

AU - Favret, Fabrice

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N2 - The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAgh) 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-TAgh mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAgh 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.

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KW - Anemia

KW - Erythropoietin

KW - Hypoxia

KW - Myocardial contractility

KW - Myocardial vascularisation

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