title: Attenuated atherogenesis in apolipoprotein E-deficient mice lacking amyloid precursor protein.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  Our findings provide evidence that lack of APP attenuates atherogenesis and leads to plaque stability.
authors.affiliation: Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Wilrijk, Belgium.
authors.forename: Tim J L
authors.initials: TJ
authors.lastname: Van De Parre
authors.forename: Pieter-Jan D F
authors.initials: PJ
authors.lastname: Guns
authors.forename: Paul
authors.initials: P
authors.lastname: Fransen
authors.forename: Wim
authors.initials: W
authors.lastname: Martinet
authors.forename: Hidde
authors.initials: H
authors.lastname: Bult
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Herman
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012422:Rupture, Spontaneous
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D003094:Collagen; D002784:Cholesterol