title: Lipid lowering and imaging protease activation in atherosclerosis.
abstract: BACKGROUND
  Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo.
  
  
  RESULTS
  ApoE(-/-) mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a (99m)Tc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle α-actin expression.
  
  
  CONCLUSIONS
  MMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis.
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Razavian
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Azariyas
authors.initials: A
authors.lastname: Challa
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Reza
authors.initials: R
authors.lastname: Golestani
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Jae-Joon
authors.initials: JJ
authors.lastname: Jung
authors.affiliation: Lantheus Medical Imaging, North Billerica, MA.
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.|VA Connecticut Healthcare System, West Haven, CT.
authors.forename: Mehran M
authors.initials: MM
authors.lastname: Sadeghi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000178:diet therapy* / Q000378:metabolism*; D003131:Combined Modality Therapy; D004041:Dietary Fats / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D004041:Dietary Fats; D000960:Hypolipidemic Agents; D020782:Matrix Metalloproteinases