Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient mice
- PMID:10938028
- DOI: 10.1161/01.atv.20.8.e26
Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient mice
Abstract
-The lipid-lowering antioxidant probucol can inhibit atherosclerosis in animals and restenosis in humans. However, probucol has been shown to promote atherosclerosis in the aortic root of apolipoprotein E-deficient (apoE-/-) mice. In the current study, we examined the effects of probucol on both lesion formation at 4 sites along the aorta and lipoprotein oxidation in the plasma and aortas of apoE-/- mice receiving a diet containing 21.2% (wt/wt) fat and 0. 15% (wt/wt) cholesterol without or with 1% (wt/wt) probucol. After 6 months, controls had developed lesions at all sites investigated. Lesion development was strongly (P=0.0001) affected by probucol, but this effect was not uniform: lesion size was increased in the aortic root but significantly decreased in the arch, the descending thoracic aorta, and proximal abdominal aorta. Plasma and aortas of probucol-treated mice contained high concentrations of probucol and its metabolites (bisphenol and diphenoquinone); increased vitamin C; markedly decreased very low density lipoprotein (but not low density lipoprotein and high density lipoprotein); and decreased cholesterol, cholesteryl esters, triglycerides, vitamin E, and oxidized lipids compared with controls. Interestingly, probucol treatment did not decrease the proportion of aortic lipids that were oxidized. Plasma vitamin C and bisphenol, but not probucol, protected plasma lipids from ex vivo oxidation by peroxyl radicals. These results show that as in other species, probucol can inhibit lesion formation in most parts of the aorta of apoE-/- mice. This effect may involve lipid oxidation-independent mechanisms localized within the vessel wall as well as lipid lowering.
Similar articles
- Processes involved in the site-specific effect of probucol on atherosclerosis in apolipoprotein E gene knockout mice.Choy K, Beck K, Png FY, Wu BJ, Leichtweis SB, Thomas SR, Hou JY, Croft KD, Mori TA, Stocker R.Choy K, et al.Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1684-90. doi: 10.1161/01.ATV.0000174125.89058.b6. Epub 2005 Jun 16.Arterioscler Thromb Vasc Biol. 2005.PMID:15961704
- Proatherogenic and antiatherogenic effects of probucol and phytosterols in apolipoprotein E-deficient mice: possible mechanisms of action.Moghadasian MH, McManus BM, Godin DV, Rodrigues B, Frohlich JJ.Moghadasian MH, et al.Circulation. 1999 Apr 6;99(13):1733-9. doi: 10.1161/01.cir.99.13.1733.Circulation. 1999.PMID:10190884
- Vitamin E combined with selenium inhibits atherosclerosis in hypercholesterolemic rabbits independently of effects on plasma cholesterol concentrations.Schwenke DC, Behr SR.Schwenke DC, et al.Circ Res. 1998 Aug 24;83(4):366-77. doi: 10.1161/01.res.83.4.366.Circ Res. 1998.PMID:9721693
- The effect of vitamin E, probucol, and lovastatin on oxidative status and aortic fatty lesions in hyperlipidemic-diabetic hamsters.El-Swefy S, Schaefer EJ, Seman LJ, van Dongen D, Sevanian A, Smith DE, Ordovas JM, El-Sweidy M, Meydani M.El-Swefy S, et al.Atherosclerosis. 2000 Apr;149(2):277-86. doi: 10.1016/s0021-9150(99)00331-7.Atherosclerosis. 2000.PMID:10729377
- Probucol as an antioxidant and antiatherogenic drug.Kuzuya M, Kuzuya F.Kuzuya M, et al.Free Radic Biol Med. 1993 Jan;14(1):67-77. doi: 10.1016/0891-5849(93)90510-2.Free Radic Biol Med. 1993.PMID:8454225Review.
Cited by
- The influence of sulforaphane on vascular health and its relevance to nutritional approaches to prevent cardiovascular disease.Evans PC.Evans PC.EPMA J. 2011 Mar;2(1):9-14. doi: 10.1007/s13167-011-0064-3. Epub 2011 Feb 12.EPMA J. 2011.PMID:23199123Free PMC article.
- Protective role of heme oxygenase-1 against inflammation in atherosclerosis.Durante W.Durante W.Front Biosci (Landmark Ed). 2011 Jun 1;16(6):2372-88. doi: 10.2741/3860.Front Biosci (Landmark Ed). 2011.PMID:21622183Free PMC article.Review.
- Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.Wu BJ, Kathir K, Witting PK, Beck K, Choy K, Li C, Croft KD, Mori TA, Tanous D, Adams MR, Lau AK, Stocker R.Wu BJ, et al.J Exp Med. 2006 Apr 17;203(4):1117-27. doi: 10.1084/jem.20052321. Epub 2006 Apr 10.J Exp Med. 2006.PMID:16606673Free PMC article.
- Dabigatran etexilate retards the initiation and progression of atherosclerotic lesions and inhibits the expression of oncostatin M in apolipoprotein E-deficient mice.Preusch MR, Ieronimakis N, Wijelath ES, Cabbage S, Ricks J, Bea F, Reyes M, van Ryn J, Rosenfeld ME.Preusch MR, et al.Drug Des Devel Ther. 2015 Sep 10;9:5203-11. doi: 10.2147/DDDT.S86969. eCollection 2015.Drug Des Devel Ther. 2015.PMID:26392754Free PMC article.
- Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root.Teupser D, Pavlides S, Tan M, Gutierrez-Ramos JC, Kolbeck R, Breslow JL.Teupser D, et al.Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17795-800. doi: 10.1073/pnas.0408096101. Epub 2004 Dec 13.Proc Natl Acad Sci U S A. 2004.PMID:15596719Free PMC article.
LinkOut - more resources
Full Text Sources
Miscellaneous