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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:713.)
© 2002 American Heart Association, Inc.

Editorials

Breaking the Plaque

Evidence for Plaque Rupture in Animal Models of Atherosclerosis

Martin R. Bennett

From the Addenbrooke’s Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, UK

Correspondence to Professor Martin R Bennett, Division of Cardiovascular Medicine, Box 110, Addenbrooke’s Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK. E-mail mrb@mole.bio.cam.ac.uk

Animal models of disease get a bad press, none more so than models of atherosclerosis. Rodents do not get atherosclerosis, and rabbits and pigs get minimal disease; only a limited range of primates gets significant atherosclerosis that resembles human lesions. The development of genetically engineered mice with disorders of lipid metabolism, such as apolipoprotein E (apoE) and LDL receptor knockout mice, was therefore a major step forward in animal models of atherosclerosis (reviewed by Smith and Breslow¹). These mice develop atherosclerosis spontaneously, albeit variable between mouse strains, ² which can be accelerated on a high cholesterol diet. The plaques that develop are widespread and reproducible and have some architectural features reminiscent of human lesions. These mice have formed the basis for a plethora of studies identifying specific molecules critical to atherosclerosis, in particular, those regulating monocyte adherence/chemotaxis and macrophage differentiation/foam cell development. Still the critics carp. The major dissent has been that lesions occur at sites very different from human lesions–the aortic root and thoracic aorta for instance. Lesions in the aortic root are also foam cell–rich, rather than smooth muscle cell–rich, may not have a single definable fibrous cap, and represent xanthomata rather than clinically important advanced lesions. Most important of all, these mice are models of atherogenesis, not advanced atherosclerosis, and they do not exhibit the single most important event in human atherosclerosis, that of plaque rupture leading to vessel occlusion.

See page 788

It now appears that the mouse may get the last laugh. In recent years, . . . [Full Text of this Article]

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