Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse

The rupture of an atherosclerotic plaque is the main underlying cause of co ronary artery thrombotic occlusion and subsequent myocardial infarction, bu t research into the causes and treatment of plaque rupture is hampered by t he lack of a suitable animal model, Although complex atherosclerotic plaque s can be induced in a number of experimental animal systems, in none of the se 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 observ ed in three male and all four female mice. In six of these seven mice, an a therosclerotic plaque rupture was found where the brachiocephalic artery br anches into the right common carotid and right subclavian arteries. The rup tures were characterised by fragmentation and loss of elastin in the fibrou s caps of relatively small and lipid-rich plaques overlying large complex l esions, with intraplaque haemorrhage. Immunocytochemical analysis revealed loss of smooth muscle cells from ruptured caps. These data suggest that lon g-term fat-feeding of apolipoprotein E knockout mice is a useful and reprod ucible model of atherosclerotic plaque rupture, and that these ruptures occ ur predominantly in the brachiocephalic artery. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.