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Published ahead of print on March 1, 2007, doi:10.1164/rccm.200612-1771OC
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American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 1290-1297, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200612-1771OC

Original Article

Chronic Intermittent Hypoxia Induces Atherosclerosis

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

1 Division of Pulmonary and Critical Care Medicine and 2 Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Vsevolod Y. Polotsky, M.D., Ph.D., Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: vpolots1{at}jhmi.edu

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/dl; 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 diet-induced dyslipidemia.

Key Words: obstructive sleep apnea • lipids • hypoxia • mouse • stearoyl-coenzyme A desaturase


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Obstructive sleep apnea is associated with atherosclerosis, and the severity of atherosclerosis correlates with the severity of hypoxia. The causal relationships between sleep apnea and atherosclerosis are unknown.

What This Study Adds to the Field
Chronic intermittent hypoxia, similar to that observed in patients with sleep apnea, causes atherosclerotic lesions in the aorta of male C57BL/6J mice, which are resistant to the disease in the absence of hypoxia.

 

Related articles in AJRCCM:

Obstructive Sleep Apnea and Atherosclerosis: A New Paradigm
Geraldo Lorenzi-Filho and Luciano F. Drager
AJRCCM 2007 175: 1219-1221. [Full Text]  



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