Chronic intermittent hypoxia induces atherosclerosis.
BACKGROUND
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.


OBJECTIVE
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.


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.
Savransky
Vladimir
V
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Nanayakkara
Ashika
A
Li
Jianguo
J
Bevans
Shannon
S
Smith
Philip L
PL
Rodriguez
Annabelle
A
Polotsky
Vsevolod Y
VY
D000818:Animals; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology*; D015984:Causality; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002908:Chronic Disease; D018450:Disease Progression; D006949:Hyperlipidemias / Q000453:epidemiology; D000860:Hypoxia / Q000150:complications* / Q000453:epidemiology; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D013230:Stearoyl-CoA Desaturase / Q000032:analysis; D013997:Time Factors
D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase