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Published ahead of print on March 1, 2007, doi:10.1164/rccm.200612-1771OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 12, June 2007, 1290-1297

A more recent version of this article appeared on June 15, 2007
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Submitted on December 6, 2006
Accepted on March 1, 2007

Chronic Intermittent Hypoxia Induces Atherosclerosis

Vladimir Savransky1, Ashika Nanayakkara1, Jianguo Li1, Shannon Bevans1, Philip L Smith1, Annabelle Rodriguez2, and Vsevolod Y Polotsky1*

1 Department of Medicine, Divisions of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA, 2 Department of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: vpolots1{at}jhmi.edu.

Rational: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia, is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established. Objective: The objective of the present study was to examine whether chronic intermittent hypoxia 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 chronic intermittent hypoxia or intermittent air (control conditions) for 12 weeks. Measurements and Main Results: Nine out of ten mice simultaneously exposed to chronic intermittent hypoxia 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 high cholesterol diet or in mice exposed to chronic intermittent hypoxia and regular diet. High cholesterol diet resulted in significant increases in serum total and LDL cholesterol levels and a decrease in HDL cholesterol. Comparing to mice exposed to intermittent air and high cholesterol diet, combined exposure to chronic intermittent hypoxia and high cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and LDL cholesterol (124 ± 4 mg/dl vs. 106 ± 6 mg/dl, p <0.05), a 2-fold 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 diet-induced dyslipidemia.
Key words: obstructive sleep apnea; lipids; hypoxia; mouse; stearoyl coenzyme A desaturase




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