title: Demonstration of an add-on effect of probucol and cilostazol on the statin-induced anti-atherogenic effects.
abstract: Statins are often prescribed for treatment of cardiovascular diseases, although there are still many patients who cannot be effectively treated by statins alone. Both probucol and cilostazol exhibit anti-atherogenic effects. In the current study, we attempted to investigate whether a probucol and cilostazol combination had any add-on effects on atorvastatin. To examine this hypothesis, we fed Japanese white rabbits with a cholesterol-rich diet supplemented with atorvastatin alone (Statin group), probucol and cilostazol (PC group), atorvastatin, probucol and cilostazol (APC group), and compared their effects on plasma lipids and aortic atherosclerosis. All three drug-treated groups had lowered total cholesterol levels compared with the vehicle group but high-density lipoproteins cholesterol levels of the atorvastatin group were higher than other groups. Although aortic atherosclerosis was significantly reduced in all drug-treated groups, the most prominent atheroprotective effect was seen in APC group (APC: 67% reduction> PC: 43% reduction> Statin group: 42% reduction over the vehicle). Morphometric analysis revealed that the reduced aortic atherosclerosis in all three groups was mainly attributed to the reduction of intimal macrophages and smooth muscle cells. These results suggest that a combination of probucol and cilostazol with statin enhances statin's anti-atherogenic functions, which may be beneficial for those patients who are less responsive to statin therapy alone.
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Yanli
authors: Y
authors: Wang
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Liang
authors: L
authors: Bai
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Yan
authors: Y
authors: Lin
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Hua
authors: H
authors: Guan
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Ninghong
authors: N
authors: Zhu
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Yulong
authors: Y
authors: Chen
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Yafeng
authors: Y
authors: Li
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Shoucui
authors: S
authors: Gao
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China.
authors: Sihai
authors: S
authors: Zhao
authors: Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi Japan.
authors: Jianglin
authors: J
authors: Fan
authors: Research Institute of Atherosclerotic Disease, and Laboratory Animal Center, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an, Shaanxi, China. liuenqi@mail.xjtu.edu.cn.
authors: Enqi
authors: E
authors: Liu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy*; D000069059:Atorvastatin; D000077407:Cilostazol; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D011341:Probucol / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D013777:Tetrazoles; D000069059:Atorvastatin; D000077407:Cilostazol; D011341:Probucol