Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 175, Issue 12, Pages 1290-1297Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200612-1771OC
Keywords
obstructive sleep apnea; lipids; hypoxia; mouse; stearoyl-coenzyme A desaturase
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Funding
- NHLBI NIH HHS [HL79554, HL80105, HL075646, HL68715] Funding Source: Medline
- NIDDK NIH HHS [DK72488] Funding Source: Medline
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Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established. Objectives: The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL/6J mice. Methods: Forty male C57BL/6J mice, 8 weeks of age, were fed either a high-cholesterol diet or a regular chow diet and subjected either to CIH or intermittent air (control conditions) for 12 weeks. Measurements and Main Results: Nine of 10 mice simultaneously exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. In contrast, atherosclerosis was not observed in mice exposed to intermittent air and a high-cholesterol diet or in mice exposed to CIH and a regular diet. A high-cholesterol diet resulted in significant increases in serum total and low-density lipoprotein cholesterol levels and a decrease in high-density lipoprotein cholesterol. Compared with mice exposed to intermittent air and a high-cholesterol diet, combined exposure to CIH and a high-cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and low-density lipoprotein cholesterol (124 4 vs. 106 6 mg/dI; p < 0.05), a twofold increase in serum lipid peroxidation, and up-regulation of an important hepatic enzyme of lipoprotein secretion, stearoyl-coenzyme A desaturase-1. Conclusions: CIH causes atherosclerosis in the presence of dietinduced dyslipidemia.
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