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Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru

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dc.contributor.author Painschab, M.S.
dc.contributor.author Malpartida, G.E.
dc.contributor.author Dávila-Roman, V.G.
dc.contributor.author Gilman, R.H.
dc.contributor.author Kolb, T.M.
dc.contributor.author León-Velarde, F.
dc.contributor.author Miranda, J.J.
dc.contributor.author Checkley, W.
dc.date.accessioned 2019-02-22T14:55:00Z
dc.date.available 2019-02-22T14:55:00Z
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12866/5702
dc.description.abstract Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for additional genetic and environmental risk factors. en_US
dc.language.iso eng
dc.publisher Mary Ann Liebert
dc.relation.ispartof urn:issn:1557-8682
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Peru en_US
dc.subject Adult en_US
dc.subject Female en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject chronic mountain sickness en_US
dc.subject Aged en_US
dc.subject Middle Aged en_US
dc.subject Altitude en_US
dc.subject Altitude Sickness en_US
dc.subject Polycythemia en_US
dc.subject Case-Control Studies en_US
dc.subject Blood Pressure en_US
dc.subject pulmonary artery en_US
dc.subject Pulmonary Artery en_US
dc.subject erythrocytosis en_US
dc.subject polycythemia en_US
dc.subject excessive erythrocytosis en_US
dc.subject erythropoietin en_US
dc.subject hypoxia en_US
dc.subject blood pressure en_US
dc.subject altitude en_US
dc.subject Biomarkers en_US
dc.subject human en_US
dc.subject adult en_US
dc.subject aged en_US
dc.subject female en_US
dc.subject male en_US
dc.subject middle aged en_US
dc.subject Article en_US
dc.subject priority journal en_US
dc.subject Hypoxia en_US
dc.subject controlled study en_US
dc.subject blood en_US
dc.subject echocardiography en_US
dc.subject altitude disease en_US
dc.subject pulmonary hypertension en_US
dc.subject biological marker en_US
dc.subject case control study en_US
dc.subject VEGF en_US
dc.subject clinical article en_US
dc.subject hypoxia inducible factor en_US
dc.subject physiology en_US
dc.subject protein expression en_US
dc.subject vasculotropin receptor 1 en_US
dc.subject enzyme linked immunosorbent assay en_US
dc.subject Erythropoietin en_US
dc.subject C reactive protein en_US
dc.subject systolic blood pressure en_US
dc.subject basic helix loop helix transcription factor en_US
dc.subject Basic Helix-Loop-Helix Transcription Factors en_US
dc.subject endothelial PAS domain-containing protein 1 en_US
dc.subject endothelin 1 en_US
dc.subject Endothelin-1 en_US
dc.subject EPO en_US
dc.subject HIF en_US
dc.subject lung artery pressure en_US
dc.subject protein blood level en_US
dc.subject Vascular Endothelial Growth Factor Receptor-1 en_US
dc.subject Vascular Endothelial Growth Factors en_US
dc.subject vasculotropin en_US
dc.title Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1089/ham.2014.1086
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE

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