Chronic intermittent hypoxia induces atherosclerosis

Am J Respir Crit Care Med. 2007 Jun 15;175(12):1290-7. doi: 10.1164/rccm.200612-1771OC. Epub 2007 Mar 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / epidemiology
  • Atherosclerosis / etiology*
  • Causality
  • Cholesterol, Dietary / administration & dosage
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Chronic Disease
  • Disease Progression
  • Hyperlipidemias / epidemiology
  • Hypoxia / complications*
  • Hypoxia / epidemiology
  • Lipid Peroxidation
  • Liver / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Stearoyl-CoA Desaturase / analysis
  • Time Factors


  • Cholesterol, Dietary
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase