Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

Paul Robach, Stefania Recalcati, Domenico Girelli, Cecilia Gelfi, Niels J. Aachmann-Andersen, Jonas J. Thomsen, Anne M. Norgaard, Alessandra Alberghini, Natascia Campostrini, Annalisa Castagna, Agnese Viganò, Paolo Santambrogio, Tibor Kempf, Kai C. Wollert, Stéphane Moutereau, Carsten Lundby, Gaetano Cairo

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Abstract

The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.

Original languageEnglish
Pages (from-to)6707-6715
Number of pages9
JournalBlood
Volume113
Issue number26
DOIs
Publication statusPublished - 2009

Fingerprint

Erythropoietin
Metabolism
Muscle
Iron
Muscles
Hepcidins
Erythropoiesis
Myoglobin
Skeletal Muscle
Growth Differentiation Factor 15
Altitude Sickness
Apoferritins
Transferrin Receptors
Muscle Proteins
Transferrin
Healthy Volunteers
Bone
Proteins
Homeostasis
Bone Marrow

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Robach, P., Recalcati, S., Girelli, D., Gelfi, C., Aachmann-Andersen, N. J., Thomsen, J. J., ... Cairo, G. (2009). Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. Blood, 113(26), 6707-6715. https://doi.org/10.1182/blood-2008-09-178095

Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. / Robach, Paul; Recalcati, Stefania; Girelli, Domenico; Gelfi, Cecilia; Aachmann-Andersen, Niels J.; Thomsen, Jonas J.; Norgaard, Anne M.; Alberghini, Alessandra; Campostrini, Natascia; Castagna, Annalisa; Viganò, Agnese; Santambrogio, Paolo; Kempf, Tibor; Wollert, Kai C.; Moutereau, Stéphane; Lundby, Carsten; Cairo, Gaetano.

In: Blood, Vol. 113, No. 26, 2009, p. 6707-6715.

Research output: Contribution to journalArticle

Robach, P, Recalcati, S, Girelli, D, Gelfi, C, Aachmann-Andersen, NJ, Thomsen, JJ, Norgaard, AM, Alberghini, A, Campostrini, N, Castagna, A, Viganò, A, Santambrogio, P, Kempf, T, Wollert, KC, Moutereau, S, Lundby, C & Cairo, G 2009, 'Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin', Blood, vol. 113, no. 26, pp. 6707-6715. https://doi.org/10.1182/blood-2008-09-178095
Robach, Paul ; Recalcati, Stefania ; Girelli, Domenico ; Gelfi, Cecilia ; Aachmann-Andersen, Niels J. ; Thomsen, Jonas J. ; Norgaard, Anne M. ; Alberghini, Alessandra ; Campostrini, Natascia ; Castagna, Annalisa ; Viganò, Agnese ; Santambrogio, Paolo ; Kempf, Tibor ; Wollert, Kai C. ; Moutereau, Stéphane ; Lundby, Carsten ; Cairo, Gaetano. / Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin. In: Blood. 2009 ; Vol. 113, No. 26. pp. 6707-6715.
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