Oxidation products of phospholipid-containing delta-9 fatty acids specifically impair the activity of tissue factor pathway inhibitor.
In the present study, we explored the active components in oxidized low-density lipoprotein (ox-LDL) that reduce the catalytic activity of tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor of the extrinsic blood coagulation pathway. The active fraction was extracted from the phospholipid fraction of ox-LDL and separated. The oxidation products of 1- and/or 2-oleoyl phosphatidylcholine (PC) or phosphatidylethanolamine were the most potent compounds, while those of arachidonyl PC possessed only a weak inhibitory effect on the TFPI activity. These oxidized phospholipids associated strongly with rTFPI containing the carboxyl-terminal domain. When rTFPI was incubated with purified oxononanoyl PC (9CHO-PC) and its carboxylic form (9COOH-PC), the catalytic activity was specifically impaired, though neither oxovaleroyl PC (5CHO-PC) nor lyso-phospholipids reduced the TFPI activity. We conclude that the oxidation products of delta-9 unsaturated phospholipid in the lipoproteins are the active components that impair the anti-coagulation activity of TFPI.
Hiraishi
Sayuri
S
Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko, Tsukui, Kanagawa 199-0195, Japan.
Horie
Shuichi
S
Seyama
Yoshiyuki
Y
D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding
D005231:Fatty Acids, Unsaturated; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010743:Phospholipids; C051928:lipoprotein-associated coagulation inhibitor; C099252:oxidized low density lipoprotein