Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits

Lipids in Health and Disease

Research

Jianglin Fan¹  Manabu Niimi¹  Yuka Keyamura²  Masanori Nozako²  Masayuki Kohashi²  Tomohiro Yoshikawa²  Reiko Yasufuku²  Takashi Koyama² 

[1] Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan;Free Radical Research Project, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan;

关键词: Atherosclerosis;    Monocyte;    Probucol;    Atorvastatin;    Hypercholesterolemia;   

DOI  :  10.1186/1476-511X-12-166

 received in 2013-09-12, accepted in 2013-10-29,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundProbucol 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.MethodsNew 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.ResultsAtorvastatin 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Niimi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.