Intimal thickening after arterial balloon injury is increased by intermittent repetitive hypoxia, but intermittent repetitive hyperoxia is not protective

Abstract

Hypoxia increases and hyperoxia decreases experimental atherosclerosis, but it is unclear if repetitive hypoxic and hyperoxic insults affect intimal thickening after arterial injury. Rabbits on 2% cholesterol diet for 6 weeks underwent balloon injury to the abdominal aorta (AA) after week 3, and were then exposed to normoxia ( n = 6), or 12 h daily of intermittent repetitive hypoxia ( n = 6) or hyperoxia ( n = 6). After week 6, damaged AA and undamaged thoracic aorta (TA) were assessed for intimal thickening and lipid content. Compared with normoxia, hypoxia and hyperoxia did not alter the rise in serum cholesterol related to cholesterol feeding. However, compared to normoxia, hypoxia markedly increased the intima-to-media ratio in AA (1.18 ± 0.09 versus 1.96 ± 0.14, P < 0.01) and TA (0.15 ± 0.02 versus 0.41 ± 0.01, P < 0.01) whereas hyperoxia had no effect on AA disease and increased intimal thickening in TA (0.26 ± 0.03, P < 0.01). Hyperoxia promoted positive arterial remodeling in both TA and AA, resulting in larger luminal size. The cholesterol content in AA was increased by hypoxia and decreased by hyperoxia, but decreased by both treatments in TA. Lipophilic antioxidants and the proportion of arterial lipids that was oxidized were not altered by hypoxia or hyperoxia. These results suggest that intermittent repetitive hyperoxia is not protective and intermittent repetitive hypoxia promotes arterial disease in normal and injured arteries independent of lipid peroxidation.