title: Combined use of probucol and cilostazol with atorvastatin attenuates atherosclerosis in moderately hypercholesterolemic rabbits.
abstract: BACKGROUND
  Atherosclerotic cardiovascular disease is one of the major diseases that seriously impacts human health. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.
  
  
  OBJECTIVE
  The current study was designed to investigate whether combined use of probucol (an anti-oxidant agent) with cilostazol (a platelet aggregation inhibitor) would increase the inhibitory effect of statins (a lipid-lowering agent) on atherosclerosis in moderately hypercholesterolemic rabbits.
  
  
  RESULTS
  Thirty Japanese white rabbits were fed with a high cholesterol diet for 12 weeks, which was supplemented with either 0.005% atorvastatin alone or 0.005% atorvastatin plus 0.3% probucol and 0.3% cilostazol. Except for high-density lipoprotein cholesterol, no difference was found in plasma lipids among vehicle, statin, and the combined treatment group. However, atherosclerotic lesions were significantly reduced by statin treatment compared with vehicle. Moreover, we found that the anti-atherogenic effect of statin was further enhanced by the combined treatment, which was due to increased anti-inflammatory and anti-oxidant properties.
  
  
  CONCLUSIONS
  These data demonstrated that combined drug treatment exhibits potent athero-protective effects via pleiotropic functions, such as anti-inflammatory and anti-oxidative stress, which is independent of the lipid-lowering effect.
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Department of Pathology, Xi'an Medical University, Xi'an, Shaanxi, 710021, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China. bailiang0922@mail.xjtu.edu.cn.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China. bailiang0922@mail.xjtu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Bai
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, 710021, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guan
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Ninghong
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Shoucui
authors.initials: S
authors.lastname: Gao
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Sun
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, 710061, China.|Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.|Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, 710021, China.
authors.forename: Enqi
authors.initials: E
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D000077407:Cilostazol; D004359:Drug Therapy, Combination; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D007249:Inflammation / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D008055:Lipids; D013777:Tetrazoles; D000069059:Atorvastatin; D000077407:Cilostazol; D011341:Probucol