dc.contributor.author |
Choy, K |
en |
dc.contributor.author |
Beck, K |
en |
dc.contributor.author |
Png, FY |
en |
dc.contributor.author |
Wu, BJ |
en |
dc.contributor.author |
Leichtweis, Steven |
en |
dc.contributor.author |
Thomas, SR |
en |
dc.contributor.author |
Hou, JY |
en |
dc.contributor.author |
Croft, KD |
en |
dc.contributor.author |
Mori, TA |
en |
dc.contributor.author |
Stocker, R |
en |
dc.date.accessioned |
2014-12-03T20:37:58Z |
en |
dc.date.issued |
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 |
http://hdl.handle.net/2292/23666 |
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 http://www.ahajournals.org/site/rights/ http://www.sherpa.ac.uk/romeo/issn/1079-5642/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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 |
http://purl.org/eprint/accessRights/RestrictedAccess |
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 |