title: Characterization of specifically oxidized apolipoproteins in mildly oxidized high density lipoprotein.
abstract: Atherosclerosis is a state of heightened oxidative stress. Oxidized LDL is present in atherosclerotic lesions and used as marker for coronary artery disease, although in human lesions lipids associated with HDL are as oxidized as those of LDL. Here we investigated specific changes occurring to apolipoprotein A-I (apoA-I) and apoA-II, as isolated HDL and human plasma undergo mild, chemically induced oxidation, or autoxidation. During such oxidation, Met residues in apoA-I and apoA-II become selectively and consecutively oxidized to their respective Met sulfoxide (MetO) forms that can be separated by HPLC. Placing plasma at -20 degrees C prevents autoxidation, whereas metal chelators and butylated hydroxytoluene offer partial protection. Independent of the oxidation conditions, apoA-I and apoA-II (dimer) with two MetO residues accumulate as relatively stable oxidation products. Compared to controls, serum samples from subjects with the endothelial cell nitric oxide synthase a/b genotype that is associated with increased coronary artery disease contain increased concentrations of apoA-I with two MetO residues. Our results show that during the early stages, oxidation of HDL gives rise to specifically oxidized forms of apoA-I and apoA-II, some of which may be useful markers of in vivo HDL oxidation, and hence potentially atherosclerosis.
authors.affiliation: The Heart Research Institute, 145 Missenden Road, Camperdown NSW 2050, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Pankhurst
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
authors.forename: David E
authors.initials: DE
authors.lastname: Wilcken
authors.forename: Georg
authors.initials: G
authors.lastname: Baernthaler
authors.forename: Ute
authors.initials: U
authors.lastname: Panzenböck
authors.forename: Mark
authors.initials: M
authors.lastname: Raftery
authors.forename: Roland
authors.initials: R
authors.lastname: Stocker
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000737:chemistry / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D010949:Plasma / Q000737:chemistry; D012907:Smoking; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III