Acclimatization to long-term hypoxia: gene expression in ovine carotid arteries

Ravi Goyal, Lawrence D. Longo

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Exposure to acute high-altitude hypoxia is associated with an increase in cerebral blood flow (CBF) as a consequence of low arterial O2 tension. However, in response to high altitude acclimatization, CBF returns to levels similar to those at sea level, and tissue blood flow is maintained by an increase in angiogenesis. Of consequence, dysregulation of the acclimatization responses and CBF can result in acute mountain sickness, acute cerebral and/or pulmonary edema. To elucidate the signal transduction pathways involved in successful acclimatization to high altitude, in ovine carotid arteries, we tested the hypothesis that high altitude-associated long-term hypoxia results in changes in gene expression of critical signaling pathways. We acclimatized nonpregnant adult sheep to 3,801 m altitude for ∼110 days and conducted oligonucleotide microarray experiments on carotid arteries. Of a total of 116 regulated genes, 58 genes were significantly upregulated and 58 genes were significantly downregulated (each >2-fold, P < 0.05). Major upregulated genes included suprabasin and myelin basic protein, whereas downregulated genes included BAG2. Several of these genes are known to activate the ERK canonical signal transduction pathway and the process of angiogenesis. We conclude that among other changes, the altered signal transduction molecules involved in high-altitude acclimatization are associated ERK activation and angiogenesis.

Original languageEnglish (US)
Pages (from-to)725-734
Number of pages10
JournalPhysiological Genomics
Volume46
Issue number19
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

Keywords

  • acute mountain sickness
  • chronic hypoxia
  • oligonucleotide microarray
  • prolonged hypoxia

ASJC Scopus subject areas

  • Physiology
  • Genetics

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