Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice

Apolipoprotein E-deficient (apoE(-/-)) and LDL receptor-deficient (LDLR-/-) mice develop extensive atherosclerosis, but the occurrence of spontaneous plaque rupture and secondary thrombosis in these models has not been establ ished. The goal of this study was to provide histological evidence of acute complications of atherosclerotic lesions in these mice and to assess their prevalence. Complications of atherosclerosis were initially studied in aor tas of control mice which died during previous intervention studies. Corona ry arteries and the aortic origin were then systematically assessed in seri al sections through the heart of apoE(-/-) and LDLR-/- mice. Aortic plaque rupture and/or thrombi were seen in 3 of 82 untreated mice from past interv ention studies. Screening of heart sections of 33 older apoE(-/-) mice (age 9-20 months) showed extensive atherosclerosis in one or more coronary arte ries of 18 animals. In three coronary arteries, the presence of blood-fille d channels within advanced atherosclerotic lesions suggested previous plaqu e disruption/thrombotic events followed by recanalization. In the aortic or igin of the same mice, four deep plaque ruptures (or erosions reaching necr otic core areas) and a large thrombus originating from the core of a disrup ted atherosclerotic lesion were observed. Although plaque ruptures/deep ero sions were far less frequent than in human populations, these observations demonstrate that spontaneous plaque rupture and secondary thrombosis do occ ur in apoE(-/-) and LDLR-/- mice. These mice may therefore be suitable for studying factors contributing to thrombotic complications of atherosclerosi s. However, the frequent absence of a clearly defined single fibrous cap in murine coronary lesions limits their usefulness as a model of fibrous cap rupture. Copyright (C) 2001 John Wiley & Sons, Ltd.