Full-length human tissue factor pathway inhibitor inhibits human activated protein C in the presence of heparin

Thrombosis Research
T Hamamoto, W Kisiel

Abstract

Previous studies have demonstrated that tissue factor pathway inhibitor (TFPI) purified from a hepatoma cell line failed to inhibit human activated protein C (APC) or human thrombin. In the present study, we have examined the ability of full-length TFPI and a truncated form of TFPI lacking the third Kunitz-type domain and C-terminal tail (TFPI1-161) to inhibit the amidolytic activity of human APC in the presence and absence of heparin. TFPI readily inhibited APC amidolytic activity only in the presence of heparin, whereas TFPI1-161 failed to inhibit APC amidolytic activity in the presence or absence of heparin. Optimal inhibition of APC by TFPI was observed at 1 U/ml heparin. The results of competition studies between factor Xa and APC for inhibition by TFPI in the presence of heparin suggested that the second Kunitz-type domain in TFPI was responsible for the inhibition of APC.

References

Aug 21, 1990·Biochemistry·G J BrozeW F Novotny
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Citations

Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·George J Broze, Thomas J Girard
Jul 2, 2005·Expert Opinion on Investigational Drugs·L ChiK P Gallagher
Oct 13, 2000·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·S I HakkiT Wright
Feb 24, 2001·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·S I HakkiT Wright

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