|
Journal of Lipid Research, Vol. 40, 1958-1966, November 1999
Copyright © 1999 by Lipid Research, Inc.
Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits
Joachim Fruebisa,
Mercedes Silvestrea,
Diane Sheltonb,
Claudio Napolia, and
Wulf Palinskia
a Departments of Medicine, University of California, San Diego, La Jolla, CA 92093
b Pathology, University of California, San Diego, La Jolla, CA 92093
Correspondence to:
Wulf Palinski
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.
Supplementary key words:
adhesion molecules, antioxidants, arteriosclerosis, immunocytochemistry, oxidation, oxidized LDL, PCR, probucol, vitamin E

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
C. S. Kim, S. J. Son, E. K. Kim, S. N. Kim, D. G. Yoo, H. S. Kim, S. W. Ryoo, S. D. Lee, K. Irani, and B. H. Jeon
Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells
Cardiovasc Res,
February 1, 2006;
69(2):
520 - 526.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Kunsch, J. Luchoomun, J. Y. Grey, L. K. Olliff, L. B. Saint, R. F. Arrendale, M. A. Wasserman, U. Saxena, and R. M. Medford
Selective Inhibition of Endothelial and Monocyte Redox-Sensitive Genes by AGI-1067: A Novel Antioxidant and Anti-Inflammatory Agent
J. Pharmacol. Exp. Ther.,
March 1, 2004;
308(3):
820 - 829.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Braun, S. Zhang, H. E. Miettinen, S. Ebrahim, T. M. Holm, E. Vasile, M. J. Post, D. M. Yoerger, M. H. Picard, J. L. Krieger, et al.
Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse
PNAS,
June 10, 2003;
100(12):
7283 - 7288.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Meydani
Vitamin E and Atherosclerosis: Beyond Prevention of LDL Oxidation
J. Nutr.,
February 1, 2001;
131(2):
366S - 368.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
C. Napoli, J. L. Witztum, F. Calara, F. de Nigris, and W. Palinski
Maternal Hypercholesterolemia Enhances Atherogenesis in Normocholesterolemic Rabbits, Which Is Inhibited by Antioxidant or Lipid-Lowering Intervention During Pregnancy : An Experimental Model of Atherogenic Mechanisms in Human Fetuses
Circ. Res.,
November 10, 2000;
87(10):
946 - 952.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Takabe, T. Kodama, T. Hamakubo, K. Tanaka, T. Suzuki, H. Aburatani, N. Matsukawa, and N. Noguchi
Anti-atherogenic Antioxidants Regulate the Expression and Function of Proteasome alpha -Type Subunits in Human Endothelial Cells
J. Biol. Chem.,
October 26, 2001;
276(44):
40497 - 40501.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|