The effect of heparin on the regulation of factor VIIa-tissue factor activity by tissue factor pathway inhibitor

被引：17

作者：

Hamamoto, T ^{[1
]}

Kisiel, W ^{[1
]}

机构：

[1] UNIV NEW MEXICO,SCH MED,DEPT PATHOL,ALBUQUERQUE,NM 87131

来源：

BLOOD COAGULATION & FIBRINOLYSIS | 1996年 / 7卷 / 04期

关键词：

tissue factor pathway inhibitor; factor VIIa tissue factor; heparin;

D O I：

10.1097/00001721-199606000-00007

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-tissue factor and factor Xa through its first and second Kunitz-type domains, respectively. Previous studies have shown that heparin binds to TFPI at two sites and enhances the inhibitory activity of TFPI towards factor Xa. We have studied the effect of heparin of the TFPI-mediated inhibition of factor VIIa-relipidated tissue factor amiodolytic activity and factor VIIa-tissue factor proteolytic activity towards factor IX and factor X on a human bladder carcinoma cell line, J82. The inhibitory activity of full-length TFPI on factor Wa-tissue factor amidolytic and proteolytic activities was greatly enhanced by heparin, whereas the inhibitory activity of a truncated form of TFPI lacking the third Kunitz-type domain and carboxy-terminal tail (TFP1-161) was not affected by heparin. Optimal inhibition of factor VIIa-tissue factor by TFPI was observed at 0.1 U/ml heparin. Heparin enhanced the inhibitory activity of TFPI towards factor Xa even in the presence of factor VIIa-tissue factor complexes in solution phase. In addition, heparin augmented the ability of TFPI to inhibit factor VIIa-tissue factor amidolytic activity in the presence of active-site mutated factor X (S376A factor X). Our collective results suggest that heparin may play a significant role in augmenting the physiological regulation of factor VIIa-tissue factor activity by TFPI.

引用

页码：470 / 476

页数：7

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