title: Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.
abstract: OBJECTIVE
  Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced ultrasound (CEU) could assess treatment effects on endothelial phenotype in early atherosclerosis.
  
  
  METHODS
  Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM)) and control microbubbles (MB(Ctr)). Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression.
  
  
  RESULTS
  Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM) in non-treated animals (MB(VCAM) 2±0.3 vs MB(Ctr) 0.7±0.2, p<0.01), but not in statin-treated animals (MB(VCAM) 0.8±0.2 vs MB(Ctr) 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM) signal).
  
  
  CONCLUSIONS
  Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.
authors.affiliation: Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
authors.forename: Elham
authors.initials: E
authors.lastname: Khanicheh
authors.forename: Martina
authors.initials: M
authors.lastname: Mitterhuber
authors.forename: Lifen
authors.initials: L
authors.lastname: Xu
authors.forename: Stéphanie P
authors.initials: SP
authors.lastname: Haeuselmann
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Kuster
authors.forename: Beat A
authors.initials: BA
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057054:Molecular Imaging; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol
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