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Low Ambient Oxygen Prevents Atherosclerosis

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NHLBI

IMMUNO-10

Authors

  • J.G. Kang
  • H.J. Sung
  • M.J. Amar
  • A.T. Remaley
  • A. Noguchi
  • D. Springer
  • P.Y. Wang
  • P.M. Hwang

Abstract

Large epidemiolgic studies show that living at high altitude, which decreases oxygen exposure, is associated with reduced cardiovascular and cancer mortality. However, some experimental data show that acute hypoxia exposure can increase atherosclerosis by worsening inflammation and blood lipid profiles. We sought to address these disparate observations by chronically controlling the oxygen exposure of ApoE-/- mice and examining its effect on atherosclerosis. Herein, we report that reducing oxygen exposure by 50% caused a marked decrease in aortic atherosclerosis, associated with the inhibition of pro-inflammatory cytokines in circulation and increased anti-inflammatory IL10 levels in aortic tissue. We further show that the expression of IL10, well established to prevent atherosclerosis, was induced by low oxygen in a hypoxia inducible factor-1α (HIF1 α) dependent manner. We propose that this anti-inflammatory mechanism may contribute to the lower incidence of ischemic heart disease in populations living at high altitudes and suggest a potential therapeutic pathway for disease prevention.

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