title: Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of tissue factor pathway inhibitor through association with its carboxy-terminal region.
abstract: Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits the initial reactions of blood coagulation. In this study, we explored the nature of active components that reduce the anticoagulant activity of TFPI in oxidized low-density lipoprotein (ox-LDL). The organic solvent-soluble fraction obtained from ox-LDL was fractionated by normal-phase HPLC. The binding profile of each fraction to TFPI showed a single peak eluting near purified oxidized phospholipid. To explore further the components in oxidized phospholipid that inhibit TFPI activity, we used oxidized phospholipids that mimic the biological activity of ox-LDL. The oxidation products of 1- and/or 2-oleoyl phosphatidylcholine or phosphatidylethanolamine were the most potent inhibitors of TFPI activity, whereas those of arachidonyl phosphatidylcholine possessed only a weak inhibitory effect on the TFPI activity. These oxidized phospholipids mainly associated with the C-terminal basic region of the TFPI molecule. The results indicate that oxidation products of delta-9 unsaturated phospholipids are candidate active components of ox-LDL that impair the function of TFPI through specific association with its C-terminal basic region.
authors.affiliation: Department of Clinical Molecular Biology, Teikyo University, Tsukui, Kanagawa, 199-0195 Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohkura
authors.forename: Sayuri
authors.initials: S
authors.lastname: Hiraishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hamuro
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Kamikubo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takano
authors.forename: Juzo
authors.initials: J
authors.lastname: Matsuda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Horie
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010743:Phospholipids; C051928:lipoprotein-associated coagulation inhibitor; C099252:oxidized low density lipoprotein