title: [18F]fluorodeoxyglucose uptake in atherosclerotic plaques is associated with reduced coronary flow reserve in mice.
abstract: OBJECTIVE
  Coronary microvascular dysfunction, observed as impaired coronary vasodilator capacity, is an early manifestation of coronary artery disease. Inflammation plays an important role in different stages of atherogenesis. To study the role of vessel wall inflammation in the development of coronary dysfunction, we compared [(18)F]fluorodeoxyglucose (FDG) uptake in the aorta and coronary flow reserve (CFR) in atherosclerotic mice.
  
  
  METHODS
  We studied healthy young C57BL/6 mice fed a normal diet (n = 7) as well as hypercholesterolemic low-density lipoprotein receptor-disrupted/apolipoprotein B100-expressing (LDLR(-/-)ApoB(100/100)) mice (n = 15) and hypercholesterolemic and diabetic LDLR(-/-)ApoB(100/100)insulinlike growth factor II-overexpressing mice (n = 14) fed a western-type diet, aged 4 to 6 months. Doppler sonography was used to measure CFR as the ratio of coronary flow velocity during isoflurane-induced hyperemia and at rest. Uptake of [(18)F]FDG into the aorta was measured by autoradiography of tissue sections.
  
  
  RESULTS
  Histologic sections showed extensive atherosclerosis in the aorta, but coronary arteries were not obstructed. Both hyperemic coronary flow velocity and CFR were reduced (P < .05) in hypercholesterolemic mice with and without diabetes in comparison to healthy young C57BL/6 controls. Among hypercholesterolemic mice, both hyperemic flow velocity and CFR inversely correlated with atherosclerotic plaque [(18)F]FDG uptake in the aorta (r = -0.73; P < .001; r = -0.63; P = .001, respectively). In a multivariate analysis, including animal weight, aortic plaque burden, plasma glucose, plasma cholesterol, and [(18)F]FDG uptake in atherosclerotic plaques, only [(18)F]FDG uptake remained an independent predictor of reduced CFR (β = 0.736; P = .001).
  
  
  CONCLUSIONS
  The inflammatory activity in atherosclerotic plaques of the aorta independently predicts reduced CFR in atherosclerotic mice without obstructive coronary artery disease. This finding suggests that atherosclerotic inflammation contributes to coronary dysfunction.
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Sauli
authors.initials: S
authors.lastname: Uotila
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Johanna M U
authors.initials: JM
authors.lastname: Silvola
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Pekka
authors.initials: P
authors.lastname: Saukko
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Suvi E
authors.initials: SE
authors.lastname: Heinonen
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.).
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Turku PET Center, Turku University Hospital, University of Turku, and Åbo Akademi University, Turku, Finland (S.U., J.M.U.S., P.N., A.R., J.K., A.S.); Department of Forensic Medicine (P.S.), Turku Center for Disease Modeling (A.R.), and Institute of Clinical Medicine (A.S.), University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland (P.N.); A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland (S.E.H., S.Y.-H.); and Heart Center, Turku University Hospital and University of Turku, Turku, Finland (A.S.). antti.saraste@utu.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
mesh_terms: D000818:Animals; D001025:Aortitis / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D053805:Fractional Flow Reserve, Myocardial; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: [18F]fluorodeoxyglucose; atherosclerosis; coronary flow reserve; coronary microvascular dysfunction; positron emission tomography; vascular ultrasound