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Thromb Haemost 2002; 87(01): 80-85
DOI: 10.1055/s-0037-1612947
Review Article
Schattauer GmbH

Oxidized Low-density Lipoprotein Associates Strongly with Carboxy-terminal Domain of Tissue Factor Pathway Inhibitor and Reduces the Catalytic Activity of the Protein

Shuichi Horie
1   Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa
,
Sayuri Hiraishi
1   Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa
,
Tsutomu Hamuro
2   The Chemo-Sero-Therapeutic Reseach Institute, Ohkubo, Kumamoto, Japan
,
Yu-ichi Kamikubo
2   The Chemo-Sero-Therapeutic Reseach Institute, Ohkubo, Kumamoto, Japan
,
Juzo Matsuda
1   Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa
› Author Affiliations
Further Information

Publication History

Received 13 June 2001

Accepted after revision 14 August 2001

Publication Date:
13 December 2017 (online)

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Summary

Tissue factor pathway inhibitor (TFPI) is a physiological protease inhibitor of the extrinsic blood coagulation pathway. Previously we have shown that TFPI associates quite rapidly with oxidized lowdensity lipoprotein (ox-LDL), with a reduction of the inhibitory activity on factor X activation. In the present study, it was found, by means of agarose gel electrophoresis, that the pre-incubation of full-length rTFPI with heparin or the carboxy (C)-terminal part (peptide 240-265) of TFPI prevented the association with ox-LDL in a dose-dependent manner. When rTFPI lacking the C-terminal basic part of the molecule (rTFPI-C) was mixed with ox-LDL, only a small amount of rTFPI-C was shifted to the position of ox-LDL on electrophoresis. Further, ox-LDL did not reduce the activity of rTFPI-C. These results indicate that the C-terminal domain of TFPI molecule plays a predominant role in the binding to ox-LDL and the binding through the C-terminal part is essential for the ox-LDL-dependent reduction of the anticoagulant activity of TFPI.

Keywords

Tissue factor pathway inhibitor - oxidized low-density lipoprotein - factor Xa generation - heparin - atherosclerosis
 

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