Processes involved in the site-specific effect of probucol on atherosclerosis in apolipoprotein E gene knockout mice

Show simple item record Choy, K en Beck, K en Png, FY en Wu, BJ en Leichtweis, Steven en Thomas, SR en Hou, JY en Croft, KD en Mori, TA en Stocker, R en 2014-12-03T20:37:58Z en 2005-08 en
dc.identifier.citation Arteriosclerosis, Thrombosis and Vascular Biology, 2005, 25 (8), pp. 1684 - 1690 en
dc.identifier.issn 1079-5642 en
dc.identifier.uri en
dc.description.abstract OBJECTIVE: To elucidate processes by which the antioxidant probucol increases lesion size at the aortic sinus and decreases atherosclerosis at more distal sites in apolipoprotein E-deficient (apoE(-/-)) mice. METHODS AND RESULTS: Male apoE(-/-) mice were fed high-fat chow with 1% (w/w) probucol or without (controls) for 6 months, before aortic sinus, arch, and descending aorta were analyzed separately for lesion size and composition. Compared with control, probucol significantly increased lesion size by 33% at the sinus, but it inhibited atherosclerosis at the descending aorta by 94%. Sites where atherosclerosis was inhibited contained substantially fewer macrophages, less lipids (cholesterol and cholesteryl esters), and endogenous antioxidant (alpha-tocopherol), but not oxidized lipids, and the extent to which probucol metabolism occurred was increased. Compared with control, aortic sinus lesions of probucol mice contained a substantially increased content of extracellular matrix, but decreased total cell and macrophage density, comparable levels of lipids and alpha-tocopherol, and decreased concentrations of oxidized lipids (cholesteryl ester hydroperoxides, F2-isoprostanes, and 7-ketocholesterol). CONCLUSIONS: Probucol affects atherosclerosis in apoE(-/-) mice independent of the accumulation of arterial lipid oxidation products, thereby dissociating the 2 processes. Rather, probucol exerts antiinflammatory activity by decreasing accumulation of macrophages in lesions, and it promotes a more stable lesion composition at the aortic sinus. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Arteriosclerosis, Thrombosis and Vascular Biology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.subject Aorta, Thoracic en
dc.subject Sinus of Valsalva en
dc.subject Macrophages en
dc.subject Animals en
dc.subject Mice en
dc.subject Mice, Mutant Strains en
dc.subject Disease Models, Animal en
dc.subject Probucol en
dc.subject Apolipoproteins E en
dc.subject Anti-Inflammatory Agents en
dc.subject Antioxidants en
dc.subject Lipid Peroxidation en
dc.subject Oxidative Stress en
dc.subject Male en
dc.subject Atherosclerosis en
dc.title Processes involved in the site-specific effect of probucol on atherosclerosis in apolipoprotein E gene knockout mice en
dc.type Journal Article en
dc.identifier.doi 10.1161/01.atv.0000174125.89058.b6 en
pubs.issue 8 en
pubs.begin-page 1684 en
pubs.volume 25 en
dc.identifier.pmid 15961704 en
pubs.end-page 1690 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 457788 en
dc.identifier.eissn 1524-4636 en
pubs.record-created-at-source-date 2014-12-04 en
pubs.dimensions-id 15961704 en

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