Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits
We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1999-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520324196 |
| _version_ | 1818596782589870080 |
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| author | Joachim Fruebis Mercedes Silvestre Diane Shelton Claudio Napoli Wulf Palinski |
| author_facet | Joachim Fruebis Mercedes Silvestre Diane Shelton Claudio Napoli Wulf Palinski |
| author_sort | Joachim Fruebis |
| collection | DOAJ |
| description | We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6–8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04–0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57.5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL. In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.—Fruebis, J., M. Silvestre, D. Shelton, C. Napoli, and W. Palinski. Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits. J. Lipid Res. 1999. 40: 1958–1966. |
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| format | Article |
| id | doaj.art-89233a49211d4857bb28c24613aa542a |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T11:37:23Z |
| publishDate | 1999-11-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-89233a49211d4857bb28c24613aa542a2022-12-21T22:33:02ZengElsevierJournal of Lipid Research0022-22751999-11-01401119581966Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbitsJoachim Fruebis0Mercedes Silvestre1Diane Shelton2Claudio Napoli3Wulf Palinski4Department of Medicine, University of California, San Diego, La Jolla, CA 92093Department of Medicine, University of California, San Diego, La Jolla, CA 92093Department of Pathology, University of California, San Diego, La Jolla, CA 92093Department of Medicine, University of California, San Diego, La Jolla, CA 92093To whom correspondence should be addressed.; Department of Medicine, University of California, San Diego, La Jolla, CA 92093We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6–8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04–0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57.5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL. In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.—Fruebis, J., M. Silvestre, D. Shelton, C. Napoli, and W. Palinski. Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits. J. Lipid Res. 1999. 40: 1958–1966.http://www.sciencedirect.com/science/article/pii/S0022227520324196adhesion moleculesantioxidantsarteriosclerosisimmunocytochemistryoxidationoxidized LDL |
| spellingShingle | Joachim Fruebis Mercedes Silvestre Diane Shelton Claudio Napoli Wulf Palinski Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits Journal of Lipid Research adhesion molecules antioxidants arteriosclerosis immunocytochemistry oxidation oxidized LDL |
| title | Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits |
| title_full | Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits |
| title_fullStr | Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits |
| title_full_unstemmed | Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits |
| title_short | Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits |
| title_sort | inhibition of vcam 1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in nzw rabbits |
| topic | adhesion molecules antioxidants arteriosclerosis immunocytochemistry oxidation oxidized LDL |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520324196 |
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