title: Chronic intermittent hypoxia induces atherosclerosis.
abstract: 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Savransky
authors.forename: Ashika
authors.initials: A
authors.lastname: Nanayakkara
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.forename: Shannon
authors.initials: S
authors.lastname: Bevans
authors.forename: Philip L
authors.initials: PL
authors.lastname: Smith
authors.forename: Annabelle
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
mesh_terms: 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
chemical_list: D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase