Low ambient oxygen prevents atherosclerosis.

Area of Science:

• Cardiovascular research
• Environmental physiology
• Molecular biology

Background:

• High-altitude living is linked to lower cardiovascular disease mortality, despite hypoxia.
• Hypoxia's role in atherosclerosis is debated, with some studies suggesting it worsens lipid metabolism and inflammation.
• ApoE-/- mice are a model for studying atherosclerosis.

Purpose of the Study:

• To investigate the effect of chronic reduced ambient oxygen exposure on atherosclerosis in ApoE-/- mice.
• To elucidate the underlying molecular mechanisms, particularly the role of interleukin-10 (IL-10).

Main Methods:

• Exposure of ApoE-/- mice to 10% oxygen (high altitude equivalent) versus 21% oxygen (sea level).
• Assessment of aortic atherosclerosis.
• Measurement of interleukin-10 (IL-10) expression.
• Utilizing IL10-/- ApoE-/- double knockout mice to assess IL-10's role.

Main Results:

• Long-term adaptation to 10% oxygen significantly decreased aortic atherosclerosis in ApoE-/- mice.
• This reduction was associated with increased expression of the anti-inflammatory cytokine IL-10.
• Mice lacking IL-10 (IL10-/- ApoE-/-) did not exhibit reduced atherosclerosis under 10% oxygen conditions.
• Hypoxia-inducible transcription factor-1α (HIF-1α) is implicated in IL-10 regulation.

Conclusions:

• Chronic exposure to low ambient oxygen decreases atherosclerosis in mice.
• The anti-atherosclerotic effect of low oxygen is mediated by increased IL-10 expression.
• This mechanism provides a potential explanation for reduced ischemic heart disease prevalence at high altitudes.