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Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project
Open accessAbstract
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. Forty-seven 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.
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“Serum iron and ferritin levels are decreased in Chuvash patients and in individuals sojourning at high altitude for 10–12 days.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [211]
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Metadata
- Authors
- 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, M. G., Mancia, G., Parati, G., & for the HIGHCARE investigators
- Affiliations
- Azienda Ospedaliera San Gerardo (IT)
- University of Milano-Bicocca (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Intrinsic LifeSciences (United States) (US)
- University of California, Los Angeles (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-03-10
- Volume
- 117
- Issue
- 10
- Pages
- 2953-2959
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2002636442
- Cited by
- 151
- References
- 40
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 6 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 10 · 2014: 21 · 2013: 14 · 2012: 7
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- Fondazione Cariplo (2009-2483)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Physiology (medical) › High Altitude and Hypoxia
- Keywords
- hepcidin, hypoxia, erythropoiesis, high altitude, iron homeostasis, erythropoietin, serum ferritin, growth differentiation factor 15, interleukin-6, iron mobilization, acute hypoxia, chronic hypoxia
- MeSH terms
- Hypoxia, Erythropoiesis, Erythropoietin, Female, Ferritins, Hematocrit, Humans, Iron, Male, Down-Regulation, Antimicrobial Cationic Peptides, Hepcidins
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