Download PDF
Thromb Haemost 2004; 92(03): 444-450
DOI: 10.1160/TH04-05-0309
Theme Issue Article
Schattauer GmbH

Role of tissue factor in haemostasis, thrombosis, angiogenesis and inflammation: lessons from low tissue factor mice

Rafal Pawlinski
1   The Scripps Research Institute, Department of Immunology, La Jolla, California, USA
,
Brian Pedersen
1   The Scripps Research Institute, Department of Immunology, La Jolla, California, USA
,
Jonathan Erlich
1   The Scripps Research Institute, Department of Immunology, La Jolla, California, USA
,
Nigel Mackman
1   The Scripps Research Institute, Department of Immunology, La Jolla, California, USA
› Author Affiliations
Further Information

Publication History

Received 13 February 2004

Accepted after revision 28 June 2004

Publication Date:
30 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Tissue factor (TF) contributes to a variety of biological processes by generating coagulation proteases and by the activation of protease activated receptors (PARs). Studies, using low TF mice, have provided us with novel insights into the role of TF in tissue-specific haemostasis. Low TF mice exhibit defects in the uterus, placenta, heart and lung, which are all tissues that normally express high levels of TF. We propose that these observed defects are primarily due to a reduction in the level of TF to below a critical threshold that is required to maintain adequate haemostasis. Nevertheless, a reduction in TF:FVIIa-dependent signaling may also reduce cell survival and/or compromise the integrity of the vasculature in these organs. Low TF mice are also a useful tool to study the role of TF and the coagulation cascade in other processes, such as thrombosis, inflammation and angiogenesis.

Keywords

Tissue factor - haemostasis - thrombosis - inflammation - angiogenesis
 

  • References

  • 1 Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: Initiation, maintenance, and regulation. Biochemistry 1991; 30: 10363-70.
    CrossrefPubMedGoogle Scholar
  • 2 Edgington TS, Mackman N, Brand K. et al. The structural biology of expression and function of tissue factor. Thromb Haemost 1991; 66: 67-79.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Hartzell S, Ryder K, Lanahan A. et al. A growth factor-responsive gene of murine BALB/c 3T3 cells encodes a protein homologous to human tissue factor. Mol Cell Biol 1989; 09: 2567-73.
    CrossrefPubMedGoogle Scholar
  • 4 Tremoli E, Camera M, Toschi V. et al. Tissue factor in atherosclerosis. Atherosclerosis 1999; 144: 273-83.
    CrossrefPubMedGoogle Scholar
  • 5 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124: 58S-68S.
    CrossrefPubMedGoogle Scholar
  • 6 Rao LVM. Tissue factor as a tumor procoagulant. Cancer Metastasis Rev 1992; 11: 249-66.
    CrossrefPubMedGoogle Scholar
  • 7 Camerer E, Huang W, Coughlin SR. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000; 97: 5255-60.
    CrossrefPubMedGoogle Scholar
  • 8 Camerer E, Kataoka H, Kahn M. et al. Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells. J Biol Chem 2002; 277: 16081-7.
    CrossrefPubMedGoogle Scholar
  • 9 Riewald M, Kravchenko V, Petrovan R. et al. Gene induction by coagulation factor Xa is mediated by activation of protease-activated receptor 1. Blood 2001; 97: 3109-16.
    CrossrefPubMedGoogle Scholar
  • 10 Riewald M, Ruf W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor. Proc Natl Acad Sci U S A 2001; 98: 7742-7.
    CrossrefPubMedGoogle Scholar
  • 11 Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407: 258-64.
    CrossrefPubMedGoogle Scholar
  • 12 Mackman N, Sawdey MS, Keeton MR. et al. Murine tissue factor gene expression in vivo: Tissue and cell specificity and regulation by lipopolysaccharide. Am J Pathol 1993; 143: 76-84.
    PubMedGoogle Scholar
  • 13 Fleck RA, Rao LVM, Rapaport SI. et al. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res 1990; 57: 765-81.
    CrossrefPubMedGoogle Scholar
  • 14 Eddleston M, de la Torre JC, Oldstone MBA. et al. Astrocytes are the primary source of tissue factor in the murine central nervous system – a role for astrocytes in cerebral haemostasis. J Clin Invest 1993; 92: 349-58.
    CrossrefPubMedGoogle Scholar
  • 15 Erlich JH, Parry GCN, Fearns C. et al. Tissue factor is required for uterine haemostasis and maintenance of the placental labyrinth during gestation. PNAS 1999; 96: 8138-43.
    CrossrefPubMedGoogle Scholar
  • 16 Luther T, Mackman N. Tissue factor in the heart. Multiple roles in haemostasis, thrombosis, and inflammation. Trends Cardiovasc Med 2001; 11: 307-12.
    CrossrefPubMedGoogle Scholar
  • 17 Mackman N. Regulation of the tissue factor gene. FASEB J 1995; 09: 883-9.
    CrossrefPubMedGoogle Scholar
  • 18 Parry GCN, Erlich JH, Carmeliet P. et al. Low levels of tissue factor are compatible with development and haemostasis in mice. J Clin Invest 1998; 101: 560-9.
    CrossrefPubMedGoogle Scholar
  • 19 Pawlinski R, Fernandes A, Kehrle B. et al. Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction. Proc Natl Acad Sci USA 2002; 99: 15333-8.
    CrossrefPubMedGoogle Scholar
  • 20 Luther T, Flössel C, Mackman N. et al. Tissue factor expression during human and mouse development. Am J Pathol 1996; 149: 101-13.
    PubMedGoogle Scholar
  • 21 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Am J Pathol 1989; 134: 1087-97.
    PubMedGoogle Scholar
  • 22 Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 1996; 97: 2440-51.
    CrossrefPubMedGoogle Scholar
  • 23 Carmeliet P, Mackman N, Moons L. et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-5.
    CrossrefPubMedGoogle Scholar
  • 24 Toomey JR, Kratzer KE, Lasky NM. et al. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88: 1583-7.
    PubMedGoogle Scholar
  • 25 Bugge TH, Xiao Q, Kombrinck KW. et al. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA 1996; 93: 6258-63.
    CrossrefPubMedGoogle Scholar
  • 26 Iwaki T, Sandoval-Cooper MJ, Paiva M. et al. Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse. Am J Pathol 2002; 160: 1021-34.
    CrossrefPubMedGoogle Scholar
  • 27 Suh TT, Holmbäck K, Jensen NJ. et al. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev 1995; 09: 2020-33.
    CrossrefPubMedGoogle Scholar
  • 28 Robertson LE, Wasserstrum N, Banez E. et al. Hereditary factor VII deficiency in pregnancy: peripartum treatment with factor VII concentrate. Am J Hematol 1992; 40: 38-41.
    CrossrefPubMedGoogle Scholar
  • 29 Goodwin TM. Congenital hypofibrinogenemia in pregnancy. Obstet Gynecol Surv 1989; 44: 157-61.
    CrossrefPubMedGoogle Scholar
  • 30 Kobayashi T, Terao T, Kojima T. et al. Congenital factor XIII deficiency with treatment of factor XIII concentrate and normal vaginal delivery. Gynecol Obstet Invest 1990; 29: 235-8.
    CrossrefPubMedGoogle Scholar
  • 31 Faulk WP, Labarrere CA, Carson SD. Tissue factor: Identification and characterization of cell types in human placentae. Blood 1990; 76: 86-96.
    PubMedGoogle Scholar
  • 32 Coan PM, Ferguson-Smith AC, Burton GJ. Developmental dynamics of the definitive mouse placenta assessed by stereology. Biol Reprod 2004; 70: 1806-13.
    CrossrefPubMedGoogle Scholar
  • 33 Isermann B, Sood R, Pawlinski R. et al. The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 2003; 09: 331-7.
    CrossrefPubMedGoogle Scholar
  • 34 McVey JH. Your bleeding heart: lessons from low tissue factor expression in mice. Trends Pharmacol Sci 2003; 24: 269-72.
    CrossrefPubMedGoogle Scholar
  • 35 Sabri A, Muske G, Zhang H. et al. Signaling properties and functions of two distinct cardiomyocyte protease-activated receptors. Circ Res 2000; 86: 1054-61.
    CrossrefPubMedGoogle Scholar
  • 36 Levi M, ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341: 586-92.
    CrossrefPubMedGoogle Scholar
  • 37 Giesen P, Rauch U, Bohrmann B. et al. Bloodborne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-5.
    CrossrefPubMedGoogle Scholar
  • 38 Marmur JD, Rossikhina M, Guha A. et al. Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. J Clin Invest 1993; 91: 2253-59.
    CrossrefPubMedGoogle Scholar
  • 39 Falati S, Liu Q, Gross P. et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197: 1585-98.
    CrossrefPubMedGoogle Scholar
  • 40 Zhang Y, Deng Y, Luther T. et al. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-7.
    CrossrefPubMedGoogle Scholar
  • 41 Abe K, Shoji M, Chen J. et al. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc Natl Acad Sci USA 1999; 96: 8663-8.
    CrossrefPubMedGoogle Scholar
  • 42 Bromberg ME, Sundaram R, Homer RJ. et al. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 1999; 82: 88-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Shoji M, Hancock WW, Abe K. et al. Activation of coagulation and angiogenesis in cancer. Immunohistochemical localization in situ of clotting proteins and vascular endothelial growth factor in human cancer. Am J Pathol 1998; 152: 399-411.
    PubMedGoogle Scholar
  • 44 Takano S, Tsuboi K, Tomono Y. et al. Tissue factor, osteopontin, αvβ3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 2000; 82: 1967-73.
    CrossrefPubMedGoogle Scholar
  • 45 Koomägi R, Volm M. Tissue-factor expression in human non-small-cell lung carcinoma measured by immunohistochemistry: correlation between tissue factor and angiogenesis. Int J Cancer 1998; 79: 19-22.
    CrossrefPubMedGoogle Scholar
  • 46 Callander NS, Varki N, Rao LVM. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
    CrossrefPubMedGoogle Scholar
  • 47 Contrino J, Hair G, Kreutzer DL. et al. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med 1996; 02: 209-15.
    CrossrefPubMedGoogle Scholar
  • 48 Luther T, Flossel C, Albrecht S. et al. Tissue factor expression in normal and abnormal mammary gland. Nat Med 1996; 02: 491-2.
    PubMedGoogle Scholar
  • 49 Connolly AJ, Ishihara H, Kahn ML. et al. Role of the thrombin receptor in development and evidence for a second receptor. Nature 1996; 381: 516-9.
    CrossrefPubMedGoogle Scholar
  • 50 Darrow AL, Fung-Leung W-P, Ye RD. et al. Biological consequences of thrombin receptor deficiency in mice. Thromb Haemost 1996; 76: 860-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Camerer E, Duong DN, Hamilton JR. et al. Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the haemostatic defect but not the embryonic lethality of prothrombin deficiency. Blood 2004; 103: 152-4.
    CrossrefPubMedGoogle Scholar
  • 52 Griffin CT, Srinivasan Y, Zheng YW. et al. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science 2001; 293: 1666-70.
    CrossrefPubMedGoogle Scholar
  • 53 Parry GCN, Mackman N. Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain. J Clin Invest 2000; 105: 1547-54.
    CrossrefPubMedGoogle Scholar
  • 54 Melis E, Moons L, De Mol M. et al. Targeted deletion of the cytosolic domain of tissue factor in mice does not affect development. Biochem Biophys Res Commun 2001; 286: 580-6.
    CrossrefPubMedGoogle Scholar
  • 55 Morrissey JH, Drake TA. Procoagulant response of the endothelium and monocytes. In: Schlag G, Redl H. Pathophysiology of shock, sepsis and organ failure. Berlin, New York: Springer-Verlag; 1993: 564-74.
    Google Scholar
  • 56 Drake TA, Cheng J, Chang A. et al. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142: 1-13.
    PubMedGoogle Scholar
  • 57 Erlich JH, Fearns C, Mathison J. et al. Lipopolysaccharide induction of tissue factor expression in rabbits. Infect Immun 1999; 67: 2540-6.
    PubMedGoogle Scholar
  • 58 Creasey AA, Chang AC, Feigen L. et al. Tissue factor pathway inhibitor reduces mortality from E. coli septic shock. J Clin Invest 1993; 91: 2850-6.
    CrossrefPubMedGoogle Scholar
  • 59 Taylor Jr. FB, Chang A, Ruf W. et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-34.
    PubMedGoogle Scholar
  • 60 Taylor FB, Chang AC, Peer G. et al. Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli. Blood 1998; 91: 1609-15.
    CrossrefPubMedGoogle Scholar
  • 61 Pawlinski R, Pedersen B, Schabbauer G. et al. Role of tissue factor and protease activated receptors in a mouse model of endotoxemia. Blood 2004; 103: 1342-7.
    PubMedGoogle Scholar