Abstract
Intermittent hypoxia (IH), the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to IH-induced atherosclerosis remains to be determined.
We studied the effects of 8 week-IH exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of ApoE−/− mice. Urinary 11-dehydrothromboxane B2 (11-dTXB2) was assessed in 50 OSA free of cardiovascular risk factor (CVRF) matched for age and body mass index with 25 controls, and 56 OSA with CVRF.
IH significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r=0.654, p=0.0003) and TXBS (r=0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in IH mice only (p=0.04). Urinary 11-dTXB2 was similar in OSA free of CVRF and controls, but was increased by 13% (p=0.007) in OSA with CVRF compared to OSA without.
Although OSA itself was not associated to increased urinary 11-dTXB2 concentration, COX-1 pathway was activated in IH exposed mice and in OSA presenting CVRF, and may contribute to IH-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.
- ERS