Characterization of specifically oxidized apolipoproteins in mildly oxidized high density lipoprotein.
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.
Pankhurst
Greg
G
The Heart Research Institute, 145 Missenden Road, Camperdown NSW 2050, Australia.
Wang
Xing Li
XL
Wilcken
David E
DE
Baernthaler
Georg
G
Panzenböck
Ute
U
Raftery
Mark
M
Stocker
Roland
R
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
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