title: Effects of Myeloperoxidase-Induced Oxidation on Antiatherogenic Functions of High-Density Lipoprotein.
abstract: High-density lipoprotein (HDL) has protective effects against the development of atherosclerosis; these effects include reverse cholesterol transport, antioxidant ability, and anti-inflammation. Myeloperoxidase (MPO) secreted by macrophages in atherosclerotic lesions generates tyrosyl radicals in apolipoprotein A-I (apoA-I) molecules, inducing the formation of apoA-I/apoA-II heterodimers through the tyrosine-tyrosine bond in HDL. Functional characterization of HDL oxidized by MPO could provide useful information about the significance of apoA-I/apoA-II heterodimers measurement. We investigated the effects of MPO-induced oxidation on the antiatherogenic functions of HDL as described above. The antioxidant ability of HDL, estimated as the effect on LDL oxidation induced by copper sulfate, was not significantly affected after MPO oxidation. HDL reduced THP-1 monocyte migration by suppressing the stimulation of human umbilical vein endothelial cells induced by lipopolysaccharide (LPS). MPO-oxidized HDL also showed inhibition of THP-1 chemotaxis, but the extent of inhibition was significantly attenuated compared to intact HDL. MPO treatment did not affect the cholesterol efflux capacity of HDL from [(3)H]-cholesterol-laden macrophages derived from THP-1 cells. The principal effect of MPO oxidation on the antiatherogenic potential of HDL would be the reduction of anti-inflammatory ability, suggesting that measurement of apoA-I/apoA-II heterodimers might be useful to estimate anti-inflammatory ability of HDL.
authors.affiliation: Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kameda
authors.affiliation: Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ohkawa
authors.affiliation: Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Yano
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Usami
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Sugano
authors.affiliation: Microbiology and Immunology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tozuka