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
Affiliations: Department of Biochemistry and Molecular Biology,
Royal Free and University College Medical School of UCL, Royal Free Campus,
Rowland Hill Street, London NW3 2PF, UK | Departments of Atherosclerosis, GlaxoSmithKline
Pharmaceuticals, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK | Neurology, Statistical Sciences, GlaxoSmithKline
Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex, CM19 5AD,
UK | Statistical Sciences, GlaxoSmithKline Pharmaceuticals,
New Frontiers Science Park (North), Harlow, Essex, CM19 5AD, UK
Note: [] Corresponding author: Dr. A Graham, Department of Biological and
Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University,
Cowcaddens Road, Glasgow G4 0BA. Tel.: +44 141 331 3722; Fax: +44 141 331 3208;
E-mail: Ann.Graham@gcal.ac.uk
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.
