Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of tissue factor pathway inhibitor through association with its carboxy-terminal region
Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of tissue factor pathway inhibitor through association with its carboxy-terminal region
复制标题
DOI：
10.1089/1523086041361686
复制
发表时间：
2004-08-01
影响因子：
6.6
通讯作者：
Horie, S
中科院分区：
文献类型：
--
作者：
Ohkura, N;Hiraishi, S;Horie, S
组织因子途径抑制物（TFPI）是一种Kunitz型蛋白酶抑制剂，可抑制血液凝固的初始反应。在这项研究中，我们探讨了性质的活性成分，降低TFPI在氧化低密度脂蛋白（ox-LDL）的抗凝活性。通过正相HPLC对从ox-LDL获得的有机溶剂可溶性级分进行分级。各组分与TFPI的结合曲线显示在纯化的氧化磷脂附近洗脱的单峰。为了进一步探索氧化磷脂中抑制TFPI活性的组分，我们使用了模拟ox-LDL生物活性的氧化磷脂。1-和/或2-油酰磷脂酰胆碱或磷脂酰乙醇胺的氧化产物是TFPI活性的最有效的抑制剂，而花生四烯酰磷脂酰胆碱的氧化产物对TFPI活性只有微弱的抑制作用。这些氧化磷脂主要与TFPI分子的C-末端碱性区域结合。结果表明，δ-9不饱和磷脂的氧化产物是ox-LDL的候选活性成分，其通过与TFPI的C-末端碱性区域特异性结合而损害TFPI的功能。
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.