Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: Data from the HIGHCARE project

Alberto Piperno, Stefania Galimberti, Raffaella Mariani, Sara Pelucchi, Giulia Ravasi, Carolina Lombardi, Grzegorz Bilo, Miriam Revera, Andrea Giuliano, Andrea Faini, Veronica Mainini, Mark Westerman, Tomas Ganz, Maria Grazia Valsecchi, Giuseppe Mancia, Gianfranco Parati

Research output: Contribution to journalArticlepeer-review


Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Fortyseven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P <.05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P <.001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting.

Original languageEnglish
Pages (from-to)2953-2959
Number of pages7
Issue number10
Publication statusPublished - Mar 10 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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