title: Regulatory metabolites of vitamin E and their putative relevance for atherogenesis.
abstract: Vitamin E is likely the most important antioxidant in the human diet and α-tocopherol is the most active isomer. α-Tocopherol exhibits anti-oxidative capacity in vitro, and inhibits oxidation of LDL. Beside this, α-tocopherol shows anti-inflammatory activity and modulates expression of proteins involved in uptake, transport and degradation of tocopherols, as well as the uptake, storage and export of lipids such as cholesterol. Despite promising anti-atherogenic features in vitro, vitamin E failed to be atheroprotective in clinical trials in humans. Recent studies highlight the importance of long-chain metabolites of α-tocopherol, which are formed as catabolic intermediate products in the liver and occur in human plasma. These metabolites modulate inflammatory processes and macrophage foam cell formation via mechanisms different than that of their metabolic precursor α-tocopherol and at lower concentrations. Here we summarize the controversial role of vitamin E as a preventive agent against atherosclerosis and point the attention to recent findings that highlight a role of these long-chain metabolites of vitamin E as a proposed new class of regulatory metabolites. We speculate that the metabolites contribute to physiological as well as pathophysiological processes.
authors.affiliation: Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Wallert
authors.affiliation: Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schmölz
authors.affiliation: Laboratory of Molecular Modeling and Chemoinformatics, Department of Chemistry, University of Perugia, Perugia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
authors.affiliation: Department of Nutritional, Food and Consumer Studies, University of Applied Sciences Fulda, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Birringer
authors.affiliation: Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorkowski
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D001711:Biotransformation; D002784:Cholesterol / Q000378:metabolism; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control; D007536:Isomerism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D024505:Tocopherols / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D002784:Cholesterol; D024505:Tocopherols
keywords: Atherosclerosis; Macrophage foam cells; α-13'-COOH; α-Tocopherol; α-Tocopherol long-chain metabolites