Low ambient oxygen prevents atherosclerosis

Large population studies have shown that living at higher altitudes, which lowers ambient oxygen exposure, is associated with reduced cardiovascular disease mortality. however, hypoxia has also been reported to promote atherosclerosis by worsening lipid metabolism and inflammation. we sought to address these disparate reports by reducing the ambient oxygen exposure of apoe−/− mice. we observed that long-term adaptation to 10 % o2 (equivalent to oxygen content at ∼5000 m), compared to 21 % o2 (room air at sea level), resulted in a marked decrease in aortic atherosclerosis in apoe−/− mice. this effect was associated with increased expression of the anti-inflammatory cytokine interleukin-10 (il-10), known to be anti-atherogenic and regulated by hypoxia-inducible transcription factor-1α (hif-1α). supporting these observations, apoe−/− mice that were deficient in il-10 (il10−/− apoe−/− double knockout) failed to show reduced atherosclerosis in 10 % oxygen. our study reveals a specific mechanism that can help explain the decreased prevalence of ischemic heart disease in populations living at high altitudes and identifies ambient oxygen exposure as a potential factor that could be modulated to alter pathogenesis.