title: Influence of apolipoprotein E genotype and dietary alpha-tocopherol on redox status and C-reactive protein levels in apolipoprotein E3 and E4 targeted replacement mice.
abstract: The molecular basis of the positive association between apoE4 genotype and CVD remains unclear. There is direct in vitro evidence indicating that apoE4 is a poorer antioxidant relative to the apoE3 isoform, with some indirect in vivo evidence also available. Therefore it was hypothesised that apoE4 carriers may benefit from alpha-tocopherol (alpha-Toc) supplementation. Targeted replacement mice expressing the human apoE3 and apoE4 were fed with a diet poor (0 mg/kg diet) or rich (200 mg/kg diet) in alpha-Toc for 12 weeks. Neither apoE genotype nor dietary alpha-Toc exerted any effects on the antioxidant defence system, including glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase activities. In addition, no differences were observed in mitogen-induced lymphocyte proliferation. alpha-Toc concentrations were modestly higher in plasma and lower in tissues of apoE4 compared with apoE3 mice, with the greatest differences evident in the lung, suggesting that an apoE4 genotype may reduce alpha-Toc delivery to tissues. A tendency towards increased plasma F2-isoprostanes in apoE4 mice was observed, while liver thiobarbituric acid-reactive substances did not differ between apoE3 and apoE4 mice. In addition, C-reactive protein (CRP) concentrations were reduced in apoE4 mice indicating that this positive effect on CRP may in part negate the increased CVD risk associated with an apoE4 genotype.
authors.affiliation: Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Hermann-Rodewald-Strasse 6, Kiel 24098, Germany.
authors.forename: Laia
authors.initials: L
authors.lastname: Jofre-Monseny
authors.forename: Patricia
authors.initials: P
authors.lastname: Huebbe
authors.forename: Inken
authors.initials: I
authors.lastname: Stange
authors.forename: Christine
authors.initials: C
authors.lastname: Boesch-Saadatmandi
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
authors.forename: Kim
authors.initials: K
authors.lastname: Jackson
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Minihane
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D004032:Diet; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008934:Mitogens / Q000276:immunology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013154:Spleen / Q000276:immunology; D024502:alpha-Tocopherol / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015415:Biomarkers; D008934:Mitogens; D002097:C-Reactive Protein; D005978:Glutathione; D024502:alpha-Tocopherol