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Atherosclerosis. 2011 Dec;219(2):425-31. doi: 10.1016/j.atherosclerosis.2011.07.122. Epub 2011 Aug 31.

Inflammation contributes to the atherogenic role of intermittent hypoxia in apolipoprotein-E knock out mice.

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1
INSERM U1042, Grenoble, F-38042, France. claire.arnaud@ujf-grenoble.fr

Abstract

RATIONALE:

Obstructive sleep apnea results in nocturnal intermittent hypoxia (IH) as a main trigger for cardiovascular morbidity, including atherosclerosis. IH induces hemodynamic, hormono-metabolic and also immuno-inflammatory alterations that could differentially contribute to atherosclerosis. Our study aimed at examining their respective contribution to the proatherogenic role of IH in atherosclerosis-prone mice.

METHODS:

Fifteen-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice fed on a high-cholesterol diet (HCD) for 6 weeks and exposed for the last 14 days to IH (21-5% FiO(2), 60s cycle, 8h/day) or air, were investigated for aortic atherosclerosis and lipid alterations. Then IH proatherogenicity was assessed in 15- and 20-week-old ApoE(-/-) mice fed on a standard-chow diet (SCD) exposed to IH or air for 14 days and assessed for atherosclerosis, lipid, hemodynamic and inflammation alterations.

RESULTS:

IH aggravated atherosclerosis in HCD-fed mice, whereas the extremely high cholesterol levels due to HCD were not different between normoxic and hypoxic animals. In SCD-fed mice, IH also aggravated atherosclerosis, more severely in 20 compared to 15-week-old animals. However, cholesterol levels that increased with IH were not different in the two SCD-fed groups. IH slightly elevated arterial blood pressure in 20-week-old animals only, and induced systemic and vascular inflammation, including increased splenocyte proliferation with decreased IL-10 secretion, and increased T-lymphocytes within atherosclerotic plaques.

CONCLUSIONS:

A short IH exposure without HCD has proatherogenic effects. In contrast to blood pressure or plasma lipids which were slightly or inconstantly affected by IH, inflammation at systemic and vascular levels appears as a potential contributing factor to IH atherogenicity.

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