title: Decreased plasma soluble erythropoietin receptor in high-altitude excessive erythrocytosis and Chronic Mountain Sickness.
abstract: Excessive erythrocytosis (EE) is the hallmark of chronic mountain sickness (CMS), a prevalent syndrome in high-altitude Andean populations. Although hypoxemia represents its underlying stimulus, why some individuals develop EE despite having altitude-normal blood erythropoietin (Epo) concentration is still unclear. A soluble form of the Epo receptor (sEpoR) has been identified in human blood and competes directly for Epo with its membrane counterpart (mEpoR). Thus, reduced levels of circulating sEpoR could lead to higher Epo availability and ultimately to EE. We characterized the relationship between Epo and sEpoR, with hematocrit and hemoglobin concentration in healthy highlanders and CMS patients at 4,340 m in Cerro de Pasco, Peru. Our results show that EE patients show decreased plasma sEpoR levels and can be subdivided into two subgroups of normal and high plasma Epo concentration for the altitude of residence, with hemoglobin concentration rising exponentially with an increasing Epo-to-sEpoR ratio (Epo/sEpoR). Also, we showed that the latter varies as an inverse exponential function of arterial pulse O2 saturation. Our findings suggests that EE is strongly associated with higher Epo/sEpoR values, leading to elevated plasma Epo availability to bind mEpoR, and thereby a stronger stimulus for augmented erythropoiesis. Differences in the altitude normal and high Epo CMS patients with a progressively higher Epo/sEpoR supports the hypothesis of the existence of two genetically different subgroups suffering from EE and possibly different degrees of adaptation to chronic high-altitude hypoxia.
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru francisco.villafuerte@upch.pe.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Villafuerte
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Macarlupú
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Anza-Ramírez
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Daniela
authors.initials: D
authors.lastname: Corrales-Melgar
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Vizcardo-Galindo
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Noemí
authors.initials: N
authors.lastname: Corante
authors.affiliation: Laboratorio de Fisiología Comparada, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Fabiola
authors.initials: F
authors.lastname: León-Velarde
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000097:blood*; D016022:Case-Control Studies; D002908:Chronic Disease; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010568:Peru; D011086:Polycythemia / Q000097:blood*; D012044:Regression Analysis
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin
keywords: Chronic Mountain Sickness; erythropoietin; excessive erythrocytosis; high-altitude; soluble erythropoietin receptor