Hamostaseologie 2006; 26(02): 147-153
DOI: 10.1055/s-0037-1616883
Original article
Schattauer GmbH

Tissue-Faktor im akuten Koronarsyndrom

Tissue factor in acute coronary syndromes
B. A. Steppich
1   Deutsches Herzzentrum München der Technischen Universität München
,
I. Ott
1   Deutsches Herzzentrum München der Technischen Universität München
› Author Affiliations
Further Information

Publication History

Publication Date:
27 December 2017 (online)

Zusammenfassung

Die Ruptur einer arteriosklerotischen Plaque mit nachfolgender Thrombusbildung und Gewebsischämie stellt das führende pathophysiologische Korrelat des akuten Koronarsyndroms dar. Gewebsthromboplastin oder Tissue-Faktor (TF) als wichtigster physiologischer Initiator der extrinsischen Gerinnungskaskade nimmt eine zentrale Rolle in der Pathogenese des akuten Koronarsyndroms ein. Das Ausmaß des thrombotischen Prozesses wird zum einen durch den Gehalt an lokalem, vaskulären TF des rupturierten Plaques zum anderen durch zirkulierenden TF moduliert. Neben seiner gut charakterisierten Bedeutung bei der Atherothrombose ist TF darüber hinaus über eine Aktivierung von Signaltransduktionskaskaden an entzündlichen Prozessen sowie am vaskulären Remodeling beteiligt. Der vorliegende Artikel zeigt die gegenwärtige Vorstellung über die Beteiligung von TF beim akuten Koronarsyndrom auf und diskutiert mögliche Konsequenzen und therapeutische Ansatzpunkte.

Summary

Rupture of an atherosclerotic plaque with subsequent thrombosis and myocardial ischemia is the pathopysiological mechanism in acute coronary syndromes. Tissue factor (TF) as the main initiator of the extrinsic coagulation cascade plays a central role in the pathogenesis of acute coronary syndromes. The extent of the thrombotic process is modulated by local vascular TF of the ruptured plaque as well as by circulating TF. In addition, TF alters signaling pathways and, thereby, contributes to inflammatory reactions and vascular remodeling. This review adresses current concepts of the role of TF in acute coronary syndromes and discusses potential consequences and therapeutic approaches.

 
  • References

  • 1 Abraham E, Reinhart K, Opal S. et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290: 238-47.
  • 2 Adrissino D, Merlini PA, Ariens R. et al. Tissuefactor antigen and activity in human coronary atherosclerotic plaques. Lancet 1997; 349: 769-71.
  • 3 Agraou B, Corseaux D, McFadden EP. et al. Effects of coronary angioplasty on monocyte tissue factor response in patients with stable or unstable angina. Thromb Res 1997; 88: 237-43.
  • 4 Aplin AE, Stewart SA, Assoian RK. et al. Integrinmediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J Cell Biol 2001; 153: 273-82.
  • 5 Ardissino D, Merlini PA, Bauer KA. et al. Thrombogenic potential of human coronary atherosclerotic plaques. Blood 2001; 98: 2726-9.
  • 6 Arnaud E, Barbalat V, Nicaud V. et al. Polymorphism in the 5`regulatory region of the tissue factor gene and the risk of myocardial infarction and venous thrombembolism: the ECTIM and PATHROS studies. Arterioscler Thromb Vasc Biol 2000; 20: 892-8.
  • 7 Bajaj MS, Bajaj SP. Tissue factor pathway inhibitor: potential therapeutic applications. Thromb Haemost 1997; 78: 471-7.
  • 8 Belaaouaj A, Li A, Wun T. et al. Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation. J Biol Chem 2000; 275: 27123-8.
  • 9 Belting M, Ahamed J, Ruf W. Signaling of the tissue factor coagulation pathway in angiogenesis and cancer. Arterioscler Thromb Vasc Biol 2005; 25: 1545-50.
  • 10 Bhattacharjee G, Ahamed J, Pedersen B. et al. Regulation of tissue factor-mediated initiation of the coagulation cascade by cell surface Grp78. Arterioscler Thromb Vasc Biol 2005; 25: 1737-43.
  • 11 Bogdanov V, Balasubramanian V, Hathcock J. et al. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9: 458-62.
  • 12 Bohrer H, Qiu F, Zimmermann T. et al. Role of NFkappaB in the mortality of sepsis. J Clin Invest 1997; 100: 972-85.
  • 13 Bombeli T, Karsan A, Tait JF. et al. Apoptotic vascular endothelial cells become procoagulant. Blood 1997; 89: 2429-42.
  • 14 Bonderman D, Temel A, Jakowitsch J. et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99: 2794-800.
  • 15 Boulanger C, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-52.
  • 16 Broze GJ. Tissue factor pathway inhibitor. Thromb Haemost 1995; 74: 90-3.
  • 17 Camera M, Giesen PL, Fallon J. et al. Cooperation between VEGF and TNF-alpha is necessary for exposure of active tissue factor on the surface of human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 531-7.
  • 18 Caplice NM, Mueske CS, Kleppe LS. et al. Presence of tissue factor pathway inhibitor in human atherosclerotic plaques is associated with reduced tissue factor activity. Circulation 1998; 98: 1051-7.
  • 19 Casciola-Rosen L, Rosen A, Petri M. et al. Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: Implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc Natl Acad Sci USA 1996; 93: 1624-9.
  • 20 DelConde I, Shrimpton CN, Thiagarajan P. et al. Tissue factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate Coagulation. Blood 2005; 106: 1604-11.
  • 21 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues: Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134: 1087-97.
  • 22 Drolllinger AG, Netser JC, Rodgers GM. Dithiocarbamates ameliorate the effects of endotoxin in a rabbit model of disseminated intravascular coagulation. Sem Thromb Hemost 1999; 25: 429-33.
  • 23 Eilertsen KE, Osterud B. The role of blood cells and their microparticles in blood coagulation. Biochem Soc Trans 2005; 33: 418-22.
  • 24 Engelmann B, Luther T, Müller I. Intravascular tissue factor pathway – a model for rapid initiation of coagulation within the blood vessel. Thromb Haemost 2003; 89: 3-8.
  • 25 Falati S, Gross P, Merrill-Skoloff G. et al. Real-time in vivo imaging of platelets, tissue factor and fibrin during atrial thrombus formation in the mouse. Nature Medicine 2002; 8: 1175-80.
  • 26 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.
  • 27 Fan ST, Mackman N, Cui MZ. et al. Integrin regulation of an inflammatory effector gene. Direct induction of the tissue factor promoter by engagement of beta 1 or alpha 4 integrin chains. J Immunol 1995; 154: 3266-74.
  • 28 Fleck RA, Rao LV, Rapaport SI. et al. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissuefactor antibody. Thromb Res 1990; 59: 421-37.
  • 29 Giesen P, Rauch U, Bohrmann B. et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-5.
  • 30 Girelli D, Russo C, Ferraresi P. et al. Polymorphism in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N Engl J Med 2000; 343: 774-80.
  • 31 Greeno EW, Bach RR, Moldow CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 1996; 75: 281-9.
  • 32 Higuchi DA, Wun TC, Likert KM. et al. The effect of leukocyte elastase on tssue factor pathway inhibitor. Blood 1992; 79: 1712-9.
  • 33 Houston DS. Tissue factor – a therapeutic target for thrombotic disorders. Expert Opin Ther Targets 2002; 6: 159-74.
  • 34 Hu P, Yan J, Sharifi T. et al. Comparison of three different targeted tissue factor fusion proteins for inducing tumor vessel thrombosis. Cancer Res 2003; 63: 5046-53.
  • 35 Jude B, Agraou B, McFadden EP. et al. Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. Circulation 1994; 90: 1662-8.
  • 36 Kaikita K, Takeya M, Ogawa H. et al. Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis. J Pathol 1999; 188: 180-8.
  • 37 Karnicki K, Owen W, Miller R. et al. Factors contributing to individual propensity for arterial thrombosis. Arterioscler Thromb Vasc Biol 2002; 22: 1495-9.
  • 38 Kato H. Tissue factor pathway inhibitor; its structure, function and clinical significance. Pol J Pharmacol 1996; 48: 67-72.
  • 39 Kim HK, Song KS, Park YS. et al. Changes of plasma tissue factor and tissue factor pathway inhibitor antigen levels and induction of tissue factor pathway inhibitor antigen levels and induction of tissue factor expression on the monocytes in coronary artery disease. Cardiology 2000; 93: 31-6.
  • 40 Lee A, Agnelli G, Buller H. et al. Dose-response study of recombinant factor Viia/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thrombembolism in patients undergoing total knee replacment. Circulation 2001; 104: 74-8.
  • 41 Leon C, Alex M, Klocke A. et al. Platelet ADP receptors contribute to the initation of intravascular coagulation. Blood 2004; 103: 594-600.
  • 42 Li A, Wun TC. Proteolysis of TFPI by plasmin: effect in TFPI activity. Thromb Haemost 1998; 80: 423-7.
  • 43 Lindmark E, Tenno T, Siegbahn A. Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression. Atheroscler Thromb Vasc Biol 2000; 20: 2322-8.
  • 44 Lupu C, Goodwin CA, Westmuckett AD. et al. Tissue factor pathway inhibitor in endothelial cells colocalizes with glycolipid microdomains/caveolae. Regulatory mechanisms of the anticoagulant properties of the endothelium. Arterioscler Thromb Vasc Biol 1997; 17: 2964-74.
  • 45 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-3.
  • 46 Mallat Z, Hugel B, Ohan J. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-53.
  • 47 Marco J, Ariens RA, Fajadet J. et al. Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris. Am J Cardiol 2000; 85: 527-31.
  • 48 Marmur JD, Thiruvikraman SV, Fyfe BS. et al. Identification of active tissue factor in human coronary atheroma. Circulation 1996; 94: 1226-32.
  • 49 McVey JH. Tissue factor pathway. Baillieres Best Pract Res Clin Haematol 1999; 12: 361-72.
  • 50 Melis E, Moons L, Arnout J. et al. Thrombophilia in mice expressing a tissue factor variant lacking its transmembrane and cytosolic domain. Biochem Biophys Res Com 2005; 333: 488-95.
  • 51 Mesri M, Altieri DC. Endothelial cell activation by leukocyte microparticles. J Immunol 161: 4382-7.
  • 52 Misumi K, Ogawa H, Yasue H. et al. Comparison of plasma tissue factor levels in unstable and stable angina. Am J Cardiol 1998; 81: 22-6.
  • 53 Nemerson Y. The tissue factor pathway of blood coagulation. Semin Hematol 1992; 29: 170-6.
  • 54 Neumann FJ, Gawaz M, Dickfeld T. et al. Antiplatelet effect of ticlopidine after coronary stenting. J Am Coll Cardiol 1997; 29: 1515-9.
  • 55 Nieuwland R, Berckmans RJ, McGregor S. et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95: 930-5.
  • 56 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC. et al. Cell-derived microparticles generated in patients during cardio-pulmonary bypass are highly procoagulant. Circulation 1997; 96: 3534-41.
  • 57 Ohkura N, Enjyoji K, Kamikubo Y. et al. A novel degradation pathway of tissue factor pathway inhibitor: incorporation into fibrin clot and degradation by thrombin. Blood 1997; 90: 1883-92.
  • 58 Osterud B, Bjorklid E. The tissue factor pathway in disseminated intravascular coagulation. Sem Thromb Hemost 2001; 27: 605-17.
  • 59 Ott I, Andrassy M, Zieglgangsberger D. et al. Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor. Blood 2001; 97: 3721-6.
  • 60 Ott I, de Waha R, Koch W. et al. Tissue factor promotor polymorphism is associated with increased risk of myocardial infarction. Atherosclerosis 2004; 177: 189-91.
  • 61 Ott I, Fischer EG, Miyagi Y. et al. A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280. J Cell Biol 1998; 140: 1241-53.
  • 62 Ott I, Malcouvier V, Schomig A. et al. Proteolysis of tissue factor pathway inhibitor-1 by thrombolysis in acute myocardial infarction. Circulation 2002; 105: 279-81.
  • 63 Ott I, Michaelis C, Schuermann M. et al. Vascular remodeling in mice lacking the cytoplasmatic domain of tissue factor. Circ Res 2005; 97: 293-8.
  • 64 Ott I, Miyagi Y, Miyazaki K. et al. Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2000; 20: 874-82.
  • 65 Ott I, Neumann FJ, Gawaz M. et al. Increased neutrophil- platelet adhesion in patients with unstable angina. Circulation 1996; 94: 1239-46.
  • 66 Ott I, Vukovitsch R, Schämig A. et al. Overexpression of glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor-1 inhibits tissue factor activity. Blood Coag Fibrinolysis 2003; 14: 539-44.
  • 67 Ott I, Weigand B, Michl R. et al. Tissue factor cytoplasmatic domain stimulates migration by activation of the GTPase Rac1 and mitogen-activated protein kinase p38. Circulation 2005; 111: 349-55.
  • 68 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.
  • 69 Ragni M, Golino P, Cirillo P. et al. Endogenous tissue factor pathway inhibitor modulates thrombus formation in an in vivo model of rabbit carotid artery stenosis and endothelial injury. Circulation 2000; 102: 113-7.
  • 70 Rauch U, Bonderman D, Bohrmann B. et al. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-5.
  • 71 Roldan V, Marin F, Fernandez P. et al. Tissue factor/tissue factor pathway inhibitor system and long-term prognosis after acute moycardial infarction. Int J Cardiol 2001; 78: 115-9.
  • 72 Rote WE, Nedelman MA, Mu DX. et al. Chimeric 7E3prevents carotid artery thrombosis in cynomolgus monkeys. Stroke 1994; 25: 1223-32.
  • 73 Ruf W. The interaction of activated factor VII with tissue factor: insight into the mechanism of cofactor- mediated activation of activated factor VII. Blood Coagul Fibrinolysis 1998; 9: S73-8.
  • 74 Sabatier F, Roux V, Anfosso F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 2002; 99: 3962-70.
  • 75 Salemink I, Franssen J, Willems GM. et al. Factor Xa cleavage of TFPI is associated with loss of anticoagulant activity. Thromb Haemost 1998; 80: 273-80.
  • 76 Serneri G, Abbate R, Gori A. Transient intermittent lymphocyte activation is resonsible for the instability of angina. Circulation 1992; 86: 790-7.
  • 77 Shet AS, Aras O, Gupta K. et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 2003; 102: 2678-83.
  • 78 Soejima H, Ogawa H, Yasue H. et al. Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation 1999; 99: 2908-13.
  • 79 Sorensen BB, Hedner U, Erhardtsen E. rFVIIai in acute coronary syndromes. Sem Vasc Med 2003; 3: 199-204.
  • 80 Steppich B, Mattisek C, Sobczyk D. et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93: 35-9.
  • 81 Suefuji H, Ogawa H, Yasue H. et al. Increased plasma tissue factor levels in acute myocardial infarction. Am Heart J 1997; 134: 253-9.
  • 82 Szotowski B, Antoniak S, Poller W. et al. Procoagulant tissue factor is released from endothelial cells in response to inflammatory stimuli. Circ Res 2005; 96: 1233-9.
  • 83 Toschi V, Gallo R, Lettino M. et al. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-9.
  • 84 Tremoli E, Camera M, Toschi V. et al. Tissue factor in atherosclerosis. Aterosclerosis 1999; 144: 273-8.
  • 85 Wilcox JN, Smith KM, Schwartz SM. et al. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-43.