Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient mice.
The increased risk of hyperlipidemia on the development of complications of atherosclerosis is well established. Cholesterol-lowering therapies lead to a decrease in the incidence of vascular thrombotic events that is out of proportion to the reduction in plaque size. This suggests that the occurrence of acute thrombosis overlying a disrupted plaque is influenced by changes in lipid levels. The influence of acute hyperlipidemia on the development of thrombosis overlying an atherosclerotic plaque in vivo has not been extensively studied. We used a murine model of vascular injury induced by a photochemical reaction to elicit thrombus formation overlying an atherosclerotic plaque. Fifteen apolipoprotein E-deficient mice were maintained on normal chow until the age of 30 weeks. Five days before the induction of thrombosis, 6 mice were started on a high fat diet, and 9 mice were continued on normal chow. Mice then underwent photochemical injury to the common carotid artery immediately proximal to the carotid bifurcation, where an atherosclerotic plaque is consistently present. Mice maintained on normal chow developed occlusive thrombi, determined by cessation of blood flow, 44+/-5 minutes (mean+/-SEM) after photochemical injury, whereas mice fed a high fat chow developed occlusive thrombosis at 27+/-3 minutes (P<0.02). Histological analysis confirmed the presence of acute thrombus formation overlying an atherosclerotic plaque. These studies demonstrate a useful model for assessing the determinants of thrombosis in the setting of atherosclerosis and show that acute elevations in plasma cholesterol facilitate thrombus formation at sites of atherosclerosis after vascular injury.
Eitzman
D T
DT
Cardiovascular Research Center, Department of Internal Medicine, University of Michigan Medical Center, Ann arbor 48109-0644, USA. deitzman@umich.edu
Westrick
R J
RJ
Xu
Z
Z
Tyson
J
J
Ginsburg
D
D
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications* / Q000235:genetics / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes; D006949:Hyperlipidemias / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D012395:Rose Bengal; D013927:Thrombosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology
D001057:Apolipoproteins E; D004041:Dietary Fats; D005456:Fluorescent Dyes; D012395:Rose Bengal; D002784:Cholesterol