title: Probucol suppresses macrophage infiltration and MMP expression in atherosclerotic plaques of WHHL rabbits.
abstract: OBJECTIVE
  Probucol is a lipid-lowering drug that is often prescribed for the treatment of familial hypercholesterolemia. However, it is not known whether probucol can change the lesion quality of atherosclerosis.
  
  
  METHODS
  We examined this possibility using WHHL rabbits, a model of human familial hypercholesterolemia. Three-month-old male WHHL rabbits were treated with either probucol(85 mg/kg/day) or atorvastatin(6 mg/kg/day) for 16 weeks, and their plasma lipid levels and atherosclerotic lesions were compared with those of a control group.
  
  
  RESULTS
  We found that probucol treatment reduced the plasma cholesterol levels, but less remarkably than atorvastatin treatment. In spite of this, probucol treatment led to a prominent reduction of aortic en face lesions by 39%(P＜0.01), whereas atorvastatin reduced these by 16%(P＞0.05), compared with those in the control. Histological examinations revealed that the aortic lesions of probucol-treated rabbits were characterized by reduced macrophages and increased smooth muscle cells compared with those from both the control and atorvastatin groups. Furthermore, probucol treatment reduced the coronary artery stenosis and increased the plaque stability.
  
  
  CONCLUSIONS
  These results suggest that probucol treatment may have beneficial effects on the plaque stability of hypercholesterolemic patients.
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liang
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bilal Waqar
authors.forename: Dedong
authors.initials: D
authors.lastname: Kang
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.forename: Yingge
authors.initials: Y
authors.lastname: Wang
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000517:prevention & control; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D011341:Probucol / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D061965:Matrix Metalloproteinase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D011341:Probucol