Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient mice.
OBJECTIVE
Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with increased cardiovascular mortality. This increased risk may be attributable to more extensive or unstable atherosclerotic plaques in subjects with OSA. We studied the effect of chronic IH in atherosclerosis-prone mice.


RESULTS
Apolipoprotein E-deficient (ApoE(-/-)) mice fed a high cholesterol diet were exposed to 4 or 12 weeks of IH and compared to intermittent air-exposed controls. At 4 weeks, IH increased plaque size in the aortic sinus and the descending aorta. At 12 weeks, atherosclerosis progressed in all groups, but more rapidly in the descending aorta of IH-exposed animals. Plaque composition was similar between IH and controls. Between 4 and 12 weeks, there were progressive increases in blood pressure, with relatively stable increases in serum lipids and arterial stiffness.


CONCLUSIONS
IH accelerates atherosclerotic plaque growth in ApoE(-/-) mice without affecting plaque composition. The mechanisms may include non-additive increases in serum lipids, and cumulative increases in blood pressure.
Jun
Jonathan
J
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, United States. jjun2@jhmi.edu
Reinke
Christian
C
Bedja
Djahida
D
Berkowitz
Dan
D
Bevans-Fonti
Shannon
S
Li
Jianguo
J
Barouch
Lili A
LA
Gabrielson
Kathleen
K
Polotsky
Vsevolod Y
VY
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood; D011673:Pulsatile Flow; D012850:Sinus of Valsalva / Q000473:pathology; D020181:Sleep Apnea, Obstructive / Q000150:complications
D001057:Apolipoproteins E; D002784:Cholesterol; D010100:Oxygen