title: Determination of myeloperoxidase-induced apoAI-apoAII heterodimers in high-density lipoprotein.
abstract: Myeloperoxidase secreted by macrophages and neutrophils in atherosclerotic lesions generates a tyrosyl radical in apolipoprotein (apo) AI, a major protein component of high-density lipoprotein (HDL), thus inducing the formation of apoAI-apoAII heterodimers. It can also cause nitration and chlorination of tyrosine residues. Determining the apoAI-apoAII heterodimer could provide useful information as to functional changes in HDL and/or the progression of atherosclerotic lesions. To this end, the apoAI-apoAII heterodimer was identified in normal human serum by immunoblotting; the band intensity was increased by treatment with myeloperoxidase. This apparent increase in heterodimer formation was quantitatively confirmed by ELISA. In normal human serum, a significant correlation between the concentrations of apoAI-apoAII heterodimer and free apoAII (r=0.763), but not free apoAI (r=0.093), was observed, indicating that heterodimer formation is likely induced on HDL particles carrying both apoAI and apoAII (Lp-AI/AII). In preliminary studies, the levels of apoAI-apoAII heterodimer were statistically higher in plasma from subjects with acute myocardial infarction (AMI) as compared to controls. These findings indicate the possibility that the apoAI-apoAII heterodimer, including nitration and chlorination modifications, may serve as an indicator of atherosclerotic lesions.
authors.affiliation: Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kameda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Usami
authors.forename: Saki
authors.initials: S
authors.lastname: Shimada
authors.forename: Go
authors.initials: G
authors.lastname: Haraguchi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Sugano
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
authors.forename: Minoru
authors.initials: M
authors.lastname: Tozuka
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood* / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000097:blood* / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry*; D009203:Myocardial Infarction / Q000097:blood* / Q000209:etiology; D009195:Peroxidase / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; D009195:Peroxidase