title: Mechanisms of oxidative damage of low density lipoprotein in human atherosclerosis.
abstract: Oxidatively damaged LDL may play a critical role in the pathogenesis of atherosclerotic vascular disease. Several pathways promote LDL oxidation in vitro but the physiologically relevant mechanisms have proven difficult to identify. Detection of stable compounds that result from specific reaction pathways has provided the first insights into the mechanism of oxidative damage in the human artery wall. Mass spectrometric analysis of protein oxidation products isolated from atherosclerotic tissue implicate tyrosyl radical, reactive nitrogen intermediates and hypochlorous acid in LDL oxidation and lesion formation in vivo. Hypochlorous acid is only generated by the phagocytic enzyme myeloperoxidase, which can also generate tyrosyl radical and reactive nitrogen intermediates. Chiral phase high-pressure liquid chromatography analysis of lipid oxidation products suggests that cellular lipoxygenases may also play a role at certain stages. In contrast, LDL isolated from atherosclerotic tissue is not enriched in protein oxidation products characteristic of free metal ions, which are the most widely studied in vitro model of LDL oxidation. These observations provide the first direct chemical evidence for reaction pathways that promote LDL oxidation in human atherosclerosis.
authors.affiliation: Division of Atherosclerosis, Nutrition and Lipid Research, St Louis, MO 63110, USA. heinecke@im.wustl.edu
authors.forename: J W
authors.initials: JW
authors.lastname: Heinecke
mesh_terms: D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008670:Metals; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D008670:Metals; D009569:Nitric Oxide; D009195:Peroxidase; D008084:Lipoxygenase