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

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.
Disease markers (Impact Factor: 2.17). 01/2005; 21(4):181-90. DOI: 10.1155/2005/394152
Source: PubMed

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 beta-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.


Available from: Annette Graham, Mar 17, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular diseases are the most common causes of death in Germany. Beside the known risk factors hypercholesteremia, hyperlipoproteinemia, diabetes mellitus, obesity, sedentary lifestyle, stress and high age, a pathophysiologically increased formation of reactive oxygen species (ROS) are discussed as cause of development of cardiovascular diseases. Nicotine adenine dinucleotide phosphate (NADPH) oxidase complexes have been identified as main source of oxidative stress and vascular superoxide anions. There are 7 known isoforms of the catalytic Nox subunit of the NADPH oxidase. In this dissertation it was shown that NADPH oxidase subunit Nox4 is the major Nox isoform in human endothelial cells. Nox4 could be localized in the perinuclear space. Overexpression of Nox4 enhanced endothelial superoxide anion formation. Furthermore, a reduction of oxidative stress could be demonstrated by chronic application of the biomechanical forces laminar shear stress and cyclic strain in endothelial cells in vitro. The observed downregulation of superoxide anion formation and upregulation of NO formation by application of biomechanical forces contribute to the positive balance between NO and superoxide anion and the vasoprotective potential of physiological shear stress and cyclic strain. Molecular cloning and functional analysis of the human Nox4 promoter revealed that an AP-1 binding site is essential for downregulation of Nox4 by laminar shear stress. On the other hand stimulation of endothelial cells and murine vessels with oxidized lipids caused an upregulation of vascular ROS production in vitro and ex vivo. In order to examine the mechanism of LDL induced ROS formation and the influence of NADPH oxidase, C57BL/6 (wild-type) and Nox2-/- mice were feed with a diet high in fat and sugar (Western-type diet) for 10 weeks. After feeding, the influence of diet on the expression of NADPH oxidase and ROS production was analyzed in the A. thoracalis. Both mice strains showed a significant upregulation of aortic ROS production in comparison to normal chow. The mRNA expression of aortic Nox4 was induced in Nox2-/- mice. Furthermore, the aortic p22phox mRNA expression was upregulated in both mice strains. The analysis of other organs (heart, kidney) showed no influence of the Western-type diet. In conclusion, the results demonstrate a major role of a Nox4 containing NADPH oxidase in the vascular radical formation in vitro and in vivo.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To understand how vitamin E fulfills its functions in membranes and lipoproteins, it is necessary to know how it associates with the lipid components of these structures and the effects its presence has on their structure and stability. Studies of model membrane systems containing vitamin E have proved to be an informative approach to address these questions. A review of the way vitamin E interacts with phospholipid bilayers, how it distributes within the structure, its motional diffusion characteristics, and orientation has been undertaken. The effect of vitamin E on membrane stability and permeability has been described. The tendency of vitamin E to form complexes with certain phospholipids is examined as is the way modulation of protein functions takes place. Finally, recent evidence relevant to the putative role of vitamin E in protecting membranes from free radical attack and the consequences of lipid oxidation in lipoproteins and membranes is examined.
    Vitamins & Hormones 02/2007; 76:67-98. DOI:10.1016/S0083-6729(07)76004-1 · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bamboo leaves (Phyllostachys pubescens Mazel ex J. Houz (Poacea)) have a long history of food and medical applications in Asia, including Japan and Korea. They have been used as a traditional medicine for centuries. We investigated the mechanism of anti-inflammatory activity of a bamboo leaf extract (BLE) on tumor necrosis factor-alpha (TNF-α)-induced monocyte adhesion in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to BLE did not inhibit cell viability or cause morphological changes at concentrations ranging from 1 µg/ml to 1 mg/ml. Treatment with 0.1 mg/ml BLE caused 63% inhibition of monocyte adhesion in TNF-α-activated HUVECs, which was associated with 38.4% suppression of vascular cell adhesion molecule-1 expression. Furthermore, TNF-α-induced reactive oxygen species generation was decreased to 47.9% in BLE treated TNF-α-activated HUVECs. BLE (0.05 mg/ml) also caused about 50% inhibition of interleukin-6 secretion from lipopolysaccharide-stimulated monocyte. The results indicate that BLE may be clinically useful as an anti-inflammatory or anti-oxidant for human cardiovascular disease including atherosclerosis.
    Nutrition research and practice 02/2013; 7(1):9-14. DOI:10.4162/nrp.2013.7.1.9 · 1.13 Impact Factor