title: Effects of age, diet, and type 2 diabetes on the development and FDG uptake of atherosclerotic plaques.
abstract: OBJECTIVE
  This study investigated the effects of age, duration of a high-fat diet, and type 2 diabetes on atherosclerotic plaque development and uptake of (18)F-fluorodeoxyglucose ((18)F-FDG) in 2 mouse models.
  
  
  BACKGROUND
  The animal's age and start time and duration of a high-fat diet have effects on plaque composition in atherosclerotic mice.
  
  
  METHODS
  The aortas of atherosclerotic low-density lipoprotein receptor deficient mice expressing only apolipoprotein B100 (LDLR(-/-)ApoB(100/100)) and atherosclerotic and diabetic mice overexpressing insulin-like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100)) were investigated at 4, 6, and 12 months of age and older after varying durations of high-fat diet. C57BL/6N mice on normal chow served as controls. Plaque size (intima-to-media ratio), macrophage density (Mac-3 staining), and plaque uptake of (18)F-FDG were studied by means of in vivo positron emission tomography/computed tomography by ex vivo autoradiography and by histological and immunohistochemical methods.
  
  
  RESULTS
  From the ages of 4 to 6 months and 12 months and older, the plaque size increased and the macrophage density decreased. Compared with the controls, the in vivo imaging showed increased aortic (18)F-FDG uptake at 4 and 6 months, but not at 12 months and older. Autoradiography showed focal (18)F-FDG uptake in plaques at all time points (average plaque-to-normal vessel wall ratio: 2.4 ± 0.4, p < 0.001) with the highest uptake in plaques with high macrophage density. There were no differences in the plaque size, macrophage density, or uptake of (18)F-FDG between LDLR(-/-)ApoB(100/100) and IGF-II/LDLR(-/-)ApoB(100/100) mice at any time point.
  
  
  CONCLUSIONS
  The 6-month-old LDLR(-/-)ApoB(100/100) and IGF-II/LDLR(-/-)ApoB(100/100) mice demonstrated highly inflamed, large, and extensive atherosclerotic plaques after 4 months of a high-fat diet, presenting a suitable model for studying the imaging of atherosclerotic plaque inflammation with (18)F-FDG. The presence of type 2 diabetes did not confound evaluation of plaque inflammation with (18)F-FDG.
authors.affiliation: Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Johanna M U
authors.initials: JM
authors.lastname: Silvola
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.forename: Iina
authors.initials: I
authors.lastname: Laitinen
authors.forename: Nina
authors.initials: N
authors.lastname: Savisto
authors.forename: V Jukka O
authors.initials: VJ
authors.lastname: Laine
authors.forename: Suvi E
authors.initials: SE
authors.lastname: Heinonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Pekka
authors.initials: P
authors.lastname: Saukko
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D001027:Aortography; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001345:Autoradiography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064847:Multimodal Imaging; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D053299:Apolipoprotein B-100; D019275:Radiopharmaceuticals; D017527:Receptor, IGF Type 2; D011973:Receptors, LDL; D019788:Fluorodeoxyglucose F18