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 journalArticle

82 Citations (Scopus)

Abstract

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
JournalBlood
Volume117
Issue number10
DOIs
Publication statusPublished - Mar 10 2011

Fingerprint

Hepcidins
Erythropoiesis
Iron
Modulation
Sea level
Ferritins
Erythropoietin
Serum
Oceans and Seas
Growth Differentiation Factor 15
Hypoxia
Hematocrit
Interleukin-6
Healthy Volunteers
Homeostasis
Blood
Down-Regulation
Oxygen
Kinetics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo : Data from the HIGHCARE project. / Piperno, Alberto; Galimberti, Stefania; Mariani, Raffaella; Pelucchi, Sara; Ravasi, Giulia; Lombardi, Carolina; Bilo, Grzegorz; Revera, Miriam; Giuliano, Andrea; Faini, Andrea; Mainini, Veronica; Westerman, Mark; Ganz, Tomas; Valsecchi, Maria Grazia; Mancia, Giuseppe; Parati, Gianfranco.

In: Blood, Vol. 117, No. 10, 10.03.2011, p. 2953-2959.

Research output: Contribution to journalArticle

Piperno, A, Galimberti, S, Mariani, R, Pelucchi, S, Ravasi, G, Lombardi, C, Bilo, G, Revera, M, Giuliano, A, Faini, A, Mainini, V, Westerman, M, Ganz, T, Valsecchi, MG, Mancia, G & Parati, G 2011, 'Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: Data from the HIGHCARE project', Blood, vol. 117, no. 10, pp. 2953-2959. https://doi.org/10.1182/blood-2010-08-299859
Piperno, Alberto ; Galimberti, Stefania ; Mariani, Raffaella ; Pelucchi, Sara ; Ravasi, Giulia ; Lombardi, Carolina ; Bilo, Grzegorz ; Revera, Miriam ; Giuliano, Andrea ; Faini, Andrea ; Mainini, Veronica ; Westerman, Mark ; Ganz, Tomas ; Valsecchi, Maria Grazia ; Mancia, Giuseppe ; Parati, Gianfranco. / Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo : Data from the HIGHCARE project. In: Blood. 2011 ; Vol. 117, No. 10. pp. 2953-2959.
@article{0b202495c7bb4be992d224fadbe5c00c,
title = "Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: Data from the HIGHCARE project",
abstract = "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.",
author = "Alberto Piperno and Stefania Galimberti and Raffaella Mariani and Sara Pelucchi and Giulia Ravasi and Carolina Lombardi and Grzegorz Bilo and Miriam Revera and Andrea Giuliano and Andrea Faini and Veronica Mainini and Mark Westerman and Tomas Ganz and Valsecchi, {Maria Grazia} and Giuseppe Mancia and Gianfranco Parati",
year = "2011",
month = "3",
day = "10",
doi = "10.1182/blood-2010-08-299859",
language = "English",
volume = "117",
pages = "2953--2959",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo

T2 - Data from the HIGHCARE project

AU - Piperno, Alberto

AU - Galimberti, Stefania

AU - Mariani, Raffaella

AU - Pelucchi, Sara

AU - Ravasi, Giulia

AU - Lombardi, Carolina

AU - Bilo, Grzegorz

AU - Revera, Miriam

AU - Giuliano, Andrea

AU - Faini, Andrea

AU - Mainini, Veronica

AU - Westerman, Mark

AU - Ganz, Tomas

AU - Valsecchi, Maria Grazia

AU - Mancia, Giuseppe

AU - Parati, Gianfranco

PY - 2011/3/10

Y1 - 2011/3/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953108427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953108427&partnerID=8YFLogxK

U2 - 10.1182/blood-2010-08-299859

DO - 10.1182/blood-2010-08-299859

M3 - Article

VL - 117

SP - 2953

EP - 2959

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -