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Abstract
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.