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

Matthew S. Painschab, Gary E. Malpartida, Victor G. Dávila-Roman, Robert H Gilman, Todd Matthew Kolb, Fabiola León-Velarde, J. Jaime Miranda, William Checkley

Research output: Contribution to journalArticle

Abstract

Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26-33, 2015. - 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 >2119 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 1070.25). 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.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalHigh Altitude Medicine and Biology
Volume16
Issue number1
DOIs
StatePublished - Mar 1 2015

Fingerprint

Polycythemia
Peru
Serum
Vascular Endothelial Growth Factor Receptor
Proteins
Erythropoietin
Pulmonary Artery
Hemoglobins
Altitude Sickness
Blood Pressure
Vascular Endothelial Growth Factor Receptor-1
Endothelin-1
Vascular Endothelial Growth Factor A
Echocardiography
Hypoxia
Chronic Disease
Enzyme-Linked Immunosorbent Assay
Mutation

Keywords

  • chronic mountain sickness
  • EPO
  • HIF
  • pulmonary hypertension
  • VEGF

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Public Health, Environmental and Occupational Health

Cite this

Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. / Painschab, Matthew S.; Malpartida, Gary E.; Dávila-Roman, Victor G.; Gilman, Robert H; Kolb, Todd Matthew; León-Velarde, Fabiola; Miranda, J. Jaime; Checkley, William.

In: High Altitude Medicine and Biology, Vol. 16, No. 1, 01.03.2015, p. 26-33.

Research output: Contribution to journalArticle

Painschab, Matthew S. ; Malpartida, Gary E. ; Dávila-Roman, Victor G. ; Gilman, Robert H ; Kolb, Todd Matthew ; León-Velarde, Fabiola ; Miranda, J. Jaime ; Checkley, William. / Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. In: High Altitude Medicine and Biology. 2015 ; Vol. 16, No. 1. pp. 26-33.
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