Biochemical and Biophysical Research Communications, Vol.298, No.4, 468-473, 2002
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. (C) 2002 Elsevier Science (USA). All rights reserved.