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

ObjectiveRecent 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 resultsApolipoprotein 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.ConclusionOur findings provide evidence that lack of APP attenuates atherogenesis and leads to plaque stability.