Oxidized Phospholipids in Oxidized Low-Density Lipoprotein Reduce the Activity of Tissue Factor Pathway Inhibitor Through Association with Its Carboxy-Terminal Region

Autor: Shuichi Horie, Hiroyuki Itabe, Tsutomu Hamuro, Naoki Ohkura, Sayuri Hiraishi, Tatsuya Takano, Juzo Matsuda, Yuichi Kamikubo
Rok vydání: 2004
Předmět:
Zdroj: Antioxidants & Redox Signaling. 6:705-712
ISSN: 1557-7716
1523-0864
Popis: 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 res...
Databáze: OpenAIRE