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Disease Markers
Volume 21 (2005), Issue 4, Pages 181-190
http://dx.doi.org/10.1155/2005/394152

Dietary Antioxidants Decrease Serum Soluble Adhesion Molecule (sVCAM-1, sICAM-1) but not Chemokine (JE/MCP-1, KC) Concentrations, and Reduce Atherosclerosis in C57BL but Not ApoE*3 Leiden Mice Fed an Atherogenic Diet

Nuala Murphy,1 David C Grimsditch,2 Martin Vidgeon-Hart,3 Pieter H.E. Groot,2 Philip Overend,4 G. Martin Benson,2 and Annette Graham1

1Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School of UCL, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
2Departments of Atherosclerosis, GlaxoSmithKline Pharmaceuticals, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK
3Neurology, Statistical Sciences, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, CM19 5AD, UK
4Statistical Sciences, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, CM19 5AD, UK

Received 5 January 2006; Accepted 5 January 2006

Copyright © 2005 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dietary antioxidants are reported to suppress cellular expression of chemokines and adhesion molecules that recruit monocytes to the artery wall during atherosclerosis. In the present study we measured the effect of feeding apoE*3 Leiden mice or their non-transgenic (C57BL) littermates with atherogenic diets either deficient in, or supplemented with, dietary antioxidants (vitamin E, vitamin C and β-carotene) for 12 weeks, on serum levels of CC (JE/MCP-1) and CXC (KC) chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1) and atherosclerotic lesion size. ApoE*3 Leiden mice developed gross hypercholesterolaemia, and markedly accelerated (10–20 fold; P < 0.0001) atherogenesis, compared with non-transgenic animals. Antioxidant consumption reduced lesion area in non-transgenic, but not apoE*3 Leiden, mice. Serum sVCAM-1 and sICAM-1 levels were significantly (P < 0.0001) increased (sVCAM-1 up to 3.9 fold; sICAM-1 up to 2.4 fold) by 4—8 weeks in all groups, and then declined. The initial increase in the concentration of adhesion molecules was reduced by 38%— 61% (P < 0.05) by antioxidant consumption, particularly in non-transgenic mice. By contrast, serum chemokine levels tended to increase more rapidly from baseline in apoE*3 Leiden mice, compared with non-transgenic animals, but were unaffected by dietary antioxidants. We conclude that dietary antioxidants reduce circulating soluble adhesion molecules and atherosclerosis in C57BL mice.