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; Sayuri Hiraishi; Tsutomu Hamuro; Yu-ichi Kamikubo; Juzo Matsuda

doi:10.1055/s-0037-1612947

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa

,

Sayuri Hiraishi

¹Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa

,

Tsutomu Hamuro

²The Chemo-Sero-Therapeutic Reseach Institute, Ohkubo, Kumamoto, Japan

,

Yu-ichi Kamikubo

²The Chemo-Sero-Therapeutic Reseach Institute, Ohkubo, Kumamoto, Japan

,

Juzo Matsuda

¹Department of Clinical Biochemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa

› Author Affiliations

Abstract

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

Full Text

References

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