title: Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits.
abstract: BACKGROUND
  Probucol and statin are often prescribed for treating atherosclerosis. These two drugs exhibit different mechanisms but it is unknown whether they have the same anti-atherogenic properties. In the current study, we examined whether these two drugs at optimal doses could inhibit the initiation of atherosclerosis in cholesterol-fed rabbits in the same way.
  
  
  METHODS
  New Zealand White rabbits were fed a cholesterol-rich diet for 5 weeks to produce the early-stage lesions of atherosclerosis. Drug-treated rabbits were administered either probucol or atorvastatin and serum lipids and aortic atherosclerotic lesions were compared with those in a control group.
  
  
  RESULTS
  Atorvastatin treatment significantly reduced serum total cholesterol levels while probucol treatment led to significant reduction of high-density lipoprotein cholesterol levels without changing total cholesterol levels compared with those in the control group. Compared with the control, probucol treatment led to 65% (p < 0.01) reduction while atorvastatin treatment led to 23% (p = 0.426) reduction of the aortic lesion area. Histological and immunohistochemical analyses revealed that the lesions of the probucol-treated group were characterized by remarkable reduction of monocyte adherence to endothelial cells and macrophage accumulation in the intima compared with those of both atorvastatin and control groups. Furthermore, low-density lipoprotein (LDL) isolated from the probucol group exhibited prominent anti-oxidative reaction, which was not present in LDL isolated from either the atorvastatin-treated or the control group.
  
  
  CONCLUSIONS
  This study suggests that probucol inhibits the initiation of atherosclerosis by reducing monocyte adherence and infiltration into the subintima. Anti-oxidization of LDL by probucol protects more effectively against early-stage lesion formation than statin-mediated lipid-lowering effects.
authors.forename: Manabu
authors.initials: M
authors.lastname: Niimi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Keyamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Nozako
authors.forename: Takashi
authors.initials: T
authors.lastname: Koyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Yasufuku
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan. jianglin@yamanashi.ac.jp.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D000069059:Atorvastatin; D002448:Cell Adhesion / Q000187:drug effects; D002784:Cholesterol / Q000009:adverse effects / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004041:Dietary Fats / Q000009:adverse effects / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006538:Heptanoic Acids / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000517:prevention & control*; D011341:Probucol / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D011341:Probucol