Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse.
The rupture of an atherosclerotic plaque is the main underlying cause of coronary artery thrombotic occlusion and subsequent myocardial infarction, but research into the causes and treatment of plaque rupture is hampered by the lack of a suitable animal model. Although complex atherosclerotic plaques can be induced in a number of experimental animal systems, in none of these is plaque rupture an established feature. We have surveyed branch points in the carotid arteries and aortas of apolipoprotein E knockout mice fed a diet supplemented with 21% lard and 0.15% cholesterol for up to 14 months. Six male and five female mice were used. Four of the male mice and four of the female mice died, after 46+/-3 weeks of feeding (range 37-59 weeks). Lumenal thrombus associated with atherosclerotic plaque rupture was observed in three male and all four female mice. In six of these seven mice, an atherosclerotic plaque rupture was found where the brachiocephalic artery branches into the right common carotid and right subclavian arteries. The ruptures were characterised by fragmentation and loss of elastin in the fibrous caps of relatively small and lipid-rich plaques overlying large complex lesions, with intraplaque haemorrhage. Immunocytochemical analysis revealed loss of smooth muscle cells from ruptured caps. These data suggest that long-term fat-feeding of apolipoprotein E knockout mice is a useful and reproducible model of atherosclerotic plaque rupture, and that these ruptures occur predominantly in the brachiocephalic artery.
Johnson
J L
JL
Bristol Heart Institute, University of Bristol, Level 7, Bristol Royal Infirmary, BS2 8HW, Bristol, UK.
Jackson
C L
CL
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood*; D001161:Arteriosclerosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D016122:Brachiocephalic Trunk / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000633:toxicity; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000097:blood*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D012307:Risk Factors; D012422:Rupture, Spontaneous
D001057:Apolipoproteins E; D004041:Dietary Fats; D002784:Cholesterol