Effect of intermittent hypoxia on atherosclerosis and cardiovascular function in apolipoprotein E‐deficient mice

Abstract

Obstructive sleep apnea causes intermittent hypoxia (IH) during sleep and contributes to cardiovascular disease. To determine the effect of IH on atherosclerosis, we exposed ApoE−/− mice fed a high cholesterol diet to 4 or 12 weeks of IH or intermittent air (IA) control and measured atherosclerotic lesions, blood pressure, cholesterol, pulse wave velocity (PWV), oxidative stress, and left ventricular (LV) function. The IH regimen consisted of a 5% O2 nadir once per minute for 12 hours/day during the light phase. At 4 weeks, IH doubled plaque size at the aortic root (197,215±24,832 vs. 89,125±25,638 µm2, p<0.05) without affecting lesions in the descending aorta. IH also increased LDL cholesterol, PWV, and LV dimensions. At 12 weeks, IH did not affect lesions at the aortic root (610,287±27,341 vs. 553,600±51,113 µm2, p=NS) but doubled plaque in the descending aorta (32.0±2.8% vs. 14.4±1.6%, p<0.01%). Cholesterol and PWV remained elevated. In addition, LV ejection fraction decreased while triglycerides and cardiac oxidative stress increased. We conclude that IH accelerates atherosclerosis in ApoE−/− mice, initially at the aortic root and later in the descending aorta. This finding is accompanied by exacerbation of dyslipidemia, impaired arterial vasomotion, and the development of LV dysfunction. Funding sources: NIH R01 HL080105, T32 HL07534, SF‐78568‐N, AHA 0765293U.