Attenuated atherogenesis in apolipoprotein E-deficient mice lacking amyloid precursor protein

Tim J L Van De Parre, Pieter-Jan D F Guns, Paul Fransen, Wim Martinet, Hidde Bult, Arnold G Herman, Guido R Y De Meyer
Atherosclerosis 2011, 216 (1): 54-8

OBJECTIVE: Recent evidence suggests that amyloid precursor protein (APP) is overexpressed in atherosclerosis-prone regions of mouse aorta. We therefore investigated in the present study whether APP has a role in the progression and composition of atherosclerotic plaques.

METHODS AND RESULTS: Apolipoprotein E-deficient (apoE(-/-)) mice were crossbred with animals lacking APP (APP(-/-)). After 16 weeks on a Western-type diet, apoE(-/-) and APP(-/-)/apoE(-/-) mice showed similar cholesterol levels. However, atherosclerotic plaque size was significantly reduced in the distal thoracic aorta (90% reduction) and abdominal aorta (75% reduction) of APP(-/-)/apoE(-/-) mice as compared to apoE(-/-). Plaques at the level of the aortic valves were not different in size, but showed a more stable phenotype in APP(-/-)/apoE(-/-) mice, as indicated by a reduced macrophage content, an increased amount of collagen and a thicker fibrous cap.

CONCLUSION: Our findings provide evidence that lack of APP attenuates atherogenesis and leads to plaque stability.

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