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Gene Review

Tfpi  -  tissue factor pathway inhibitor

Mus musculus

Synonyms: A630013F22Rik, AW552122, EPI, Extrinsic pathway inhibitor, LACI, ...
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Disease relevance of Tfpi


High impact information on Tfpi

  • A genetically engineered hybrid protein consisting of the light chain of factor Xa and the first Kunitz-type inhibitor domain of LACI is shown to directly inhibit the activity of the factor VIIa-TF catalytic complex [5].
  • Thus, the rescue of TFPIdelta/delta embryos, either by an accompanying homozygous or heterozygous FVII deficiency, suggests that diminishment of FVII activity precludes the need for TFPI-mediated inhibition of the FVIIa/tissue factor coagulation pathway during embryogenesis [1].
  • A balance between tissue factor and tissue factor pathway inhibitor is required for embryonic development and hemostasis in adult mice [6].
  • Conversely, a decrease in TFPI levels dose-dependently prolonged the survival of low-TF mice and rescued the hemorrhagic defects in the lung and placenta but not in the heart or uterus [6].
  • Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity [7].

Chemical compound and disease context of Tfpi

  • Taken together, these data indicated that local VSMC-specific TFPI overexpression attenuated ferric chloride-induced thrombosis without systemic or hemostatic effects [4].

Biological context of Tfpi


Anatomical context of Tfpi


Associations of Tfpi with chemical compounds

  • Prolongation of the PT occurred only moderately and linearly with increasing concentrations of heparin in LACI-depleted plasma [13].
  • Placental protein 5 (PP5)/tissue factor pathway inhibitor-2 (TFPI-2) is a new homologue of TFPI, which contains three tandemly repeated Kunitz-type proteinase inhibitory (KPI) domains and potently inhibits the extrinsic blood coagulation cascade [14].
  • Overexpression of TFPI inhibited neointimal formation (P=0.038), resulting in enhanced luminal area (P=0.001) 4 weeks after flow cessation [15].
  • Phosphoamino acid analysis of the purified 32P-LACI established that the phosphorylation occurred on (a) serine residue(s) [16].
  • LACI isolated from the conditioned media of HepG2 cells grown in the presence of [32P]orthophosphate was observed to be covalently phosphorylated [16].

Regulatory relationships of Tfpi


Other interactions of Tfpi


Analytical, diagnostic and therapeutic context of Tfpi


  1. Factor VII deficiency rescues the intrauterine lethality in mice associated with a tissue factor pathway inhibitor deficit. Chan, J.C., Carmeliet, P., Moons, L., Rosen, E.D., Huang, Z.F., Broze, G.J., Collen, D., Castellino, F.J. J. Clin. Invest. (1999) [Pubmed]
  2. Tissue factor pathway inhibitor reduces experimental lung metastasis of B16 melanoma. Amirkhosravi, A., Meyer, T., Chang, J.Y., Amaya, M., Siddiqui, F., Desai, H., Francis, J.L. Thromb. Haemost. (2002) [Pubmed]
  3. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Westrick, R.J., Bodary, P.F., Xu, Z., Shen, Y.C., Broze, G.J., Eitzman, D.T. Circulation (2001) [Pubmed]
  4. The effect of vascular smooth muscle cell-targeted expression of tissue factor pathway inhibitor in a murine model of arterial thrombosis. Pan, S., Kleppe, L.S., Witt, T.A., Mueske, C.S., Simari, R.D. Thromb. Haemost. (2004) [Pubmed]
  5. Inhibition of factor VIIa-tissue factor coagulation activity by a hybrid protein. Girard, T.J., MacPhail, L.A., Likert, K.M., Novotny, W.F., Miletich, J.P., Broze, G.J. Science (1990) [Pubmed]
  6. A balance between tissue factor and tissue factor pathway inhibitor is required for embryonic development and hemostasis in adult mice. Pedersen, B., Holscher, T., Sato, Y., Pawlinski, R., Mackman, N. Blood (2005) [Pubmed]
  7. Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity. Hembrough, T.A., Ruiz, J.F., Swerdlow, B.M., Swartz, G.M., Hammers, H.J., Zhang, L., Plum, S.M., Williams, M.S., Strickland, D.K., Pribluda, V.S. Blood (2004) [Pubmed]
  8. Gene targeting in hemostasis. tissue factor pathway inhibitor. Chan, J.C. Front. Biosci. (2001) [Pubmed]
  9. Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity. Pinotti, M., Bertolucci, C., Portaluppi, F., Colognesi, I., Frigato, E., Foà, A., Bernardi, F. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  10. Activated factor X and thrombin formation triggered by tissue factor on endothelial cell matrix in a flow model: effect of the tissue factor pathway inhibitor. van 't Veer, C., Hackeng, T.M., Delahaye, C., Sixma, J.J., Bouma, B.N. Blood (1994) [Pubmed]
  11. Tissue factor pathway inhibitor deficiency enhances neointimal proliferation and formation in a murine model of vascular remodelling. Singh, R., Pan, S., Mueske, C.S., Witt, T.A., Kleppe, L.S., Peterson, T.E., Caplice, N.M., Simari, R.D. Thromb. Haemost. (2003) [Pubmed]
  12. Cloning, expression, and characterization of mouse tissue factor pathway inhibitor (TFPI). Chang, J.Y., Monroe, D.M., Oliver, J.A., Liles, D.K., Roberts, H.R. Thromb. Haemost. (1998) [Pubmed]
  13. Lipoprotein-associated coagulation inhibitor (LACI) is a cofactor for heparin: synergistic anticoagulant action between LACI and sulfated polysaccharides. Wun, T.C. Blood (1992) [Pubmed]
  14. Cloning of the cDNA encoding mouse PP5/TFPI-2 and mapping of the gene to chromosome 6. Miyagi, Y., Yasumitsu, H., Mizushima, H., Koshikawa, N., Matsuda, Y., Itoh, H., Hori, T.A., Aoki, I., Misugi, K., Miyazaki, K. DNA Cell Biol. (1996) [Pubmed]
  15. Role for tissue factor pathway in murine model of vascular remodeling. Singh, R., Pan, S., Mueske, C.S., Witt, T., Kleppe, L.S., Peterson, T.E., Slobodova, A., Chang, J.Y., Caplice, N.M., Simari, R.D. Circ. Res. (2001) [Pubmed]
  16. Endogenous phosphorylation of the lipoprotein-associated coagulation inhibitor at serine-2. Girard, T.J., McCourt, D., Novotny, W.F., MacPhail, L.A., Likert, K.M., Broze, G.J. Biochem. J. (1990) [Pubmed]
  17. Down-regulation of murine tissue factor pathway inhibitor mRNA by endotoxin and tumor necrosis factor-alpha in vitro and in vivo. Shimokawa, T., Yamamoto, K., Kojima, T., Saito, H. Thromb. Res. (2000) [Pubmed]
  18. The low density lipoprotein receptor-related protein can function independently from heparan sulfate proteoglycans in tissue factor pathway inhibitor endocytosis. Warshawsky, I., Herz, J., Broze, G.J., Schwartz, A.L. J. Biol. Chem. (1996) [Pubmed]
  19. TFPIbeta, a second product from the mouse tissue factor pathway inhibitor (TFPI) gene. Chang, J.Y., Monroe, D.M., Oliver, J.A., Roberts, H.R. Thromb. Haemost. (1999) [Pubmed]
  20. Human tissue factor pathway inhibitor fused to CD4 binds both FXa and TF/FVIIa at the cell surface. Riesbeck, K., Dorling, A., Kemball-Cook, G., McVey, J.H., Jones, M., Tuddenham, E.G., Lechler, R.I. Thromb. Haemost. (1997) [Pubmed]
  21. Role of heparan sulfate proteoglycans in the uptake and degradation of tissue factor pathway inhibitor-coagulation factor Xa complexes. Ho, G., Broze, G.J., Schwartz, A.L. J. Biol. Chem. (1997) [Pubmed]
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