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Tissue Factor Pathway Inhibitor: Structure and Function

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Recent Advances in Thrombosis and Hemostasis 2008

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Abstract

Tissue factor pathway inhibitor (TFPI) is a protease inhibitor with three tandem Kunitz-type inhibitor domains that inhibits the tissue factor (TF)-initiated blood coagulation cascade reactions by forming a complex with factor VIIa/TF via the first Kunitz-type inhibitor domain and with factor Xa via the second Kunitz-type inhibitor domain. The third Kunitz-type inhibitor domain of TFPI has no ability to inhibit protease but plays an important role in the functions of TFPI. After the discovery of TFPI, another inhibitor with three tandem Kunitz-type inhibitor domains was isolated and named as TFPI-2. The first TFPI was then named as TFPI-1. However, TFPI-2 is not the inhibitor for the initiation of the tissue factor pathway. TFPI-2 is now thought most likely to have functions clearly different from those of TFPI-1.

In this review, TFPI-1 is simply written as TFPI. Referring to the most recent literature, the structure and function of TFPI has been reviewed. Two functions of TFPI (i.e., inhibition of the TF-initiated blood coagulation pathway and inhibition of proliferation of vascular wall cells) are discussed. The relation of the plasma TFPI level to various diseases and the prospects for clinical application of TFPI are also discussed. The structure and function of TFPI-2 are briefly summarized.

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Authors and Affiliations

  1. National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan

    Hisao Kato

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Editors and Affiliations

  1. Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenzo Tanaka M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  2. Department of Biochemistry, University of Washington, J317 Health Science Center, Box 357350, Seattle, WA, 98195, USA

    Earl W. Davie Ph.D. (Professor) (Professor)

  3. School of Medicine, Internal Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Yasuo Ikeda M.D., Ph.D. (Professor) (Professor)

  4. Department of Biology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Sadaaki Iwanaga Ph.D. (Professor Emeritus) (Professor Emeritus)

  5. Department of Medicine, Nagoya University, 26 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hidehiko Saito M.D., Ph.D. (Professor Emeritus) (Professor Emeritus)

  6. Pathophysiological and Experimental Division, Department of Pathology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Katsuo Sueishi M.D., Ph.D. (Professor) (Professor)

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Kato, H. (2008). Tissue Factor Pathway Inhibitor: Structure and Function. In: Tanaka, K., Davie, E.W., Ikeda, Y., Iwanaga, S., Saito, H., Sueishi, K. (eds) Recent Advances in Thrombosis and Hemostasis 2008. Springer, Tokyo. https://doi.org/10.1007/978-4-431-78847-8_8

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