Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness.

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 8502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1601 (Electronic) Linking ISSN: 01617567 NLM ISO Abbreviation: J Appl Physiol (1985) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, MD : American Physiological Society, c1985-
    • Subject Terms:
      Altitude Sickness/*blood ; Altitude Sickness/*metabolism ; Receptors, Erythropoietin/*blood ; Receptors, Erythropoietin/*metabolism ; Sleep/*physiology; Adult ; Aged ; Altitude ; Altitude Sickness/physiopathology ; Androgens/blood ; Chronic Disease ; Hematocrit/methods ; Humans ; Hypoxia/blood ; Hypoxia/metabolism ; Hypoxia/physiopathology ; Male ; Middle Aged ; Oxygen/metabolism ; Peru ; Polycythemia/metabolism ; Polycythemia/physiopathology ; Testosterone/blood ; Young Adult
    • Abstract:
      Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia.
      (Copyright © 2016 the American Physiological Society.)
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    • Grant Information:
      097275/Z/11/Z United Kingdom Wellcome Trust
    • Contributed Indexing:
      Keywords: Andes; Chronic Mountain Sickness; excessive erythrocytosis; sleep; soluble erythropoietin receptor
    • Accession Number:
      0 (Androgens)
      0 (Receptors, Erythropoietin)
      3XMK78S47O (Testosterone)
      S88TT14065 (Oxygen)
    • Publication Date:
      Date Created: 20160430 Date Completed: 20171214 Latest Revision: 20181113
    • Publication Date:
      20250114
    • Accession Number:
      PMC4967249
    • Accession Number:
      10.1152/japplphysiol.00107.2016
    • Accession Number:
      27125843