title: Plaque rupture and thrombosis are reduced by lowering cholesterol levels and crystallization with ezetimibe and are correlated with fluorodeoxyglucose positron emission tomography.
abstract: OBJECTIVE
  This study evaluated effects of lipid lowering with ezetimibe on plaque burden and associated cholesterol crystallization and inflammation in a rabbit model of plaque disruption and thrombosis.
  
  
  RESULTS
  Atherosclerotic rabbits (Group I, n=10 without; Group II, n=12 with ezetimibe, 1 mg/kg per day) were pharmacologically triggered for plaque disruption. Fluorodeoxyglucose positron emission tomography, RAM 11 macrophage staining, and serum inflammatory markers detected arterial inflammation. Serum and aortic wall cholesterol levels were measured, and thrombus area was planimetered. Cholesterol crystal density on aortic surface was scored (0 to +3) by scanning electron microscopy. Serum and aortic wall cholesterol, plaque area, and thrombosis area were significantly lower in Group II versus Group I (83.4±106.4 versus 608±386 mg/dL, P=0.002; 3.12±1.40 versus 9.39±5.60 mg/g, P=0.003; 10.84±1.6 versus 17.48±1.8 mm(2), P<0.001; and 0.05±0.15 versus 0.72±0.58 mm(2), P=0.01, respectively). There were significant correlations between crystal density and plaque area (r=0.75, P<0.003) and between crystal density and RAM 11 (r=0.82, P<0.001). Scanning electron microscopy demonstrated that there were fewer crystals in Group II versus Group I (+1.2±0.61 versus +2.4±0.63, P<0.001) and less inflammation detected by fluorodeoxyglucose positron emission tomography and RAM 11 (P<0.004 and P<0.04, respectively).
  
  
  CONCLUSIONS
  Lowering cholesterol levels with ezetimibe reduced plaque burden, crystallization, and inflammation, preventing plaque disruption and thrombosis.
authors.affiliation: Division of Cardiology, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Roshan
authors.initials: R
authors.lastname: Patel
authors.forename: Abed
authors.initials: A
authors.lastname: Janoudi
authors.forename: Ameeth
authors.initials: A
authors.lastname: Vedre
authors.forename: Kusai
authors.initials: K
authors.lastname: Aziz
authors.forename: Umesh
authors.initials: U
authors.lastname: Tamhane
authors.forename: Jack
authors.initials: J
authors.lastname: Rubinstein
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Abela
authors.forename: Kevin
authors.initials: K
authors.lastname: Berger
authors.forename: George S
authors.initials: GS
authors.lastname: Abela
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001011:Aorta / Q000648:ultrastructure; D001384:Azetidines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood*; D003460:Crystallization; D000069438:Ezetimibe; D019788:Fluorodeoxyglucose F18; D008297:Male; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D049268:Positron-Emission Tomography; D011817:Rabbits; D019275:Radiopharmaceuticals; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002097:C-Reactive Protein; D002784:Cholesterol; D000069438:Ezetimibe