The Role of Tissue Factor in Atherothrombosis and Coronary Artery Disease: Insights into Platelet Tissue Factor

Abstract

The contribution of vessel wall-derived tissue factor (TF) to atherothrombosis is well established, whereas the pathophysiological relevance of the blood-borne TF is still a matter of debate, and controversies on the presence of platelet-associated TF still exist. In the past 15 years, several studies have documented the presence of TF in human platelets, the capacity of human platelets to use TF mRNA to make de novo protein synthesis, and the increase in the percentage of TF positive platelets in pathological conditions such as coronary artery disease (CAD). The exposure of vessel wall-derived TF at the site of vascular injury would play its main role in the initiation phase, whereas the blood-borne TF carried by platelets would be involved in the propagation phase of thrombus formation. More recent data indicate that megakaryocytes are committed to release into the bloodstream a well-defined number of TF-carrying platelets, which represents only a fraction of the whole platelet population. These findings are in line with the evidence that platelets are heterogeneous in their functions and only a subset of them is involved in the hemostatic process. In this review we summarize the existing knowledge on platelet associated TF and speculate on its relevance to physiology and to atherothrombosis and CAD.

Keywords

tissue factor - platelets - megakaryocytes - atherothrombosis - coronary artery disease

• References

• 1 Fisher KL, Gorman CM, Vehar GA, O'Brien DP, Lawn RM. Cloning and expression of human tissue factor cDNA. Thromb Res 1987; 48 (1) 89-99
• 2 Scarpati EM, Wen D, Broze Jr GJ , et al. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry 1987; 26 (17) 5234-5238
• 3 Morrissey JH, Fakhrai H, Edgington TS. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell 1987; 50 (1) 129-135
• 4 Spicer EK, Horton R, Bloem L , et al. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proc Natl Acad Sci U S A 1987; 84 (15) 5148-5152
• 5 Giesen PL, Rauch U, Bohrmann B , et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A 1999; 96 (5) 2311-2315
• 6 Rauch U, Nemerson Y. Circulating tissue factor and thrombosis. Curr Opin Hematol 2000; 7 (5) 273-277
• 7 Tremoli E, Camera M, Toschi V, Colli S. Tissue factor in atherosclerosis. Atherosclerosis 1999; 144 (2) 273-283
• 8 van der Wal AC, Li X, de Boer OJ. Tissue factor expression in the morphologic spectrum of vulnerable atherosclerotic plaques. Semin Thromb Hemost 2006; 32 (1) 40-47
• 9 Taubman MB, Fallon JT, Schecter AD , et al. Tissue factor in the pathogenesis of atherosclerosis. Thromb Haemost 1997; 78 (1) 200-204
• 10 Asada Y, Marutsuka K, Hatakeyama K , et al. The role of tissue factor in the pathogenesis of thrombosis and atherosclerosis. J Atheroscler Thromb 1998; 4 (3) 135-139
• 11 Moons AH, Levi M, Peters RJ. Tissue factor and coronary artery disease. Cardiovasc Res 2002; 53 (2) 313-325
• 12 Owens III AP, Mackman N. Role of tissue factor in atherothrombosis. Curr Atheroscler Rep 2012; 14 (5) 394-401
• 13 Bouchard BA, Mann KG, Butenas S. No evidence for tissue factor on platelets. Blood 2010; 116 (5) 854-855
• 14 Camera M, Brambilla M, Toschi V, Tremoli E. Tissue factor expression on platelets is a dynamic event. Blood 2010; 116 (23) 5076-5077
• 15 Camera M, Brambilla M, Boselli D , et al. Functionally active platelets do express tissue factor. Blood 2012; 119 (18) 4339-4341
• 16 Østerud B, Olsen JO. Human platelets do not express tissue factor. Thromb Res 2013; 132 (1) 112-115
• 17 Østerud B. Tissue factor expression in blood cells. Thromb Res 2010; 125 (Suppl. 01) S31-S34
• 18 Fukuda C, Iijima K, Nakamura K. Measuring tissue factor (factor III) activity in plasma. Clin Chem 1989; 35 (9) 1897-1900
• 19 Key NS, Slungaard A, Dandelet L , et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood 1998; 91 (11) 4216-4223
• 20 Albrecht S, Kotzsch M, Siegert G , et al. Detection of circulating tissue factor and factor VII in a normal population. Thromb Haemost 1996; 75 (5) 772-777
• 21 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 (22) 2908-2913
• 22 Suefuji H, Ogawa H, Yasue H , et al. Increased plasma tissue factor levels in acute myocardial infarction. Am Heart J 1997; 134 (2 Pt 1): 253-259
• 23 Misumi K, Ogawa H, Yasue H , et al. Comparison of plasma tissue factor levels in unstable and stable angina pectoris. Am J Cardiol 1998; 81 (1) 22-26
• 24 Gando S, Nanzaki S, Sasaki S, Aoi K, Kemmotsu O. Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock. Crit Care Med 1998; 26 (12) 2005-2009
• 25 Amengual O, Atsumi T, Khamashta MA, Hughes GR. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 1998; 79 (2) 276-281
• 26 Asakura H, Kamikubo Y, Goto A , et al. Role of tissue factor in disseminated intravascular coagulation. Thromb Res 1995; 80 (3) 217-224
• 27 Carey MJ, Rodgers GM. Disseminated intravascular coagulation: clinical and laboratory aspects. Am J Hematol 1998; 59 (1) 65-73
• 28 Hugel B, Socié G, Vu T , et al. Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 1999; 93 (10) 3451-3456
• 29 Jy W, Horstman LL, Arce M, Ahn YS. Clinical significance of platelet microparticles in autoimmune thrombocytopenias. J Lab Clin Med 1992; 119 (4) 334-345
• 30 Warkentin TE, Hayward CP, Boshkov LK , et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood 1994; 84 (11) 3691-3699
• 31 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC , et al. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997; 96 (10) 3534-3541
• 32 Nieuwland R, Berckmans RJ, McGregor S , et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95 (3) 930-935
• 33 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 (1) 170-175
• 34 Rauch U, Nemerson Y. Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000; 10 (4) 139-143
• 35 Zillmann A, Luther T, Müller I , et al. Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation. Biochem Biophys Res Commun 2001; 281 (2) 603-609
• 36 Siddiqui FA, Desai H, Amirkhosravi A, Amaya M, Francis JL. The presence and release of tissue factor from human platelets. Platelets 2002; 13 (4) 247-253
• 37 Camera M, Frigerio M, Toschi V , et al. Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. Arterioscler Thromb Vasc Biol 2003; 23 (9) 1690-1696
• 38 Müller I, Klocke A, Alex M , et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 2003; 17 (3) 476-478
• 39 Brambilla M, Camera M, Colnago D , et al. Tissue factor in patients with acute coronary syndromes: expression in platelets, leukocytes, and platelet-leukocyte aggregates. Arterioscler Thromb Vasc Biol 2008; 28 (5) 947-953
• 40 Fink L, Hölschermann H, Kwapiszewska G , et al. Characterization of platelet-specific mRNA by real-time PCR after laser-assisted microdissection. Thromb Haemost 2003; 90 (4) 749-756
• 41 Schwertz H, Tolley ND, Foulks JM , et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 2006; 203 (11) 2433-2440
• 42 Panes O, Matus V, Sáez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood 2007; 109 (12) 5242-5250
• 43 Gerrits AJ, Koekman CA, van Haeften TW, Akkerman JW. Platelet tissue factor synthesis in type 2 diabetic patients is resistant to inhibition by insulin. Diabetes 2010; 59 (6) 1487-1495
• 44 Falanga A, Marchetti M, Vignoli A , et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Hematol 2007; 35 (5) 702-711
• 45 Tilley RE, Holscher T, Belani R, Nieva J, Mackman N. Tissue factor activity is increased in a combined platelet and microparticle sample from cancer patients. Thromb Res 2008; 122 (5) 604-609
• 46 Weyrich AS, Dixon DA, Pabla R , et al. Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc Natl Acad Sci U S A 1998; 95 (10) 5556-5561
• 47 Lindemann S, Tolley ND, Dixon DA , et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154 (3) 485-490
• 48 Evangelista V, Manarini S, Di Santo A , et al. De novo synthesis of cyclooxygenase-1 counteracts the suppression of platelet thromboxane biosynthesis by aspirin. Circ Res 2006; 98 (5) 593-595
• 49 Camera M, Brambilla M, Facchinetti L , et al. Tissue factor and atherosclerosis: not only vessel wall-derived TF, but also platelet-associated TF. Thromb Res 2012; 129 (3) 279-284
• 50 Brambilla M, Facchinetti L, Canzano P , et al. Human megakaryocytes express Tissue Factor and deliver it to a subset of shedded platelets where it contributes to thrombin generation. Thromb Haemost 2015; 114 (3) 579-592
• 51 Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood 2003; 101 (6) 2285-2293
• 52 Bugert P, Dugrillon A, Günaydin A, Eichler H, Klüter H. Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost 2003; 90 (4) 738-748
• 53 Hillmann AG, Harmon S, Park SD, O'brien J, Shields DC, Kenny D. Comparative RNA expression analyses from small-scale, single-donor platelet samples. J Thromb Haemost 2006; 4 (2) 349-356
• 54 Muszbek L, Adány R, Mikkola H. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function. Crit Rev Clin Lab Sci 1996; 33 (5) 357-421
• 55 Jayo A, Conde I, Lastres P, Jiménez-Yuste V, González-Manchón C. New insights into the expression and role of platelet factor XIII-A. J Thromb Haemost 2009; 7 (7) 1184-1191
• 56 Takenaka T, Kuribayashi K, Tsukiyama M, Nakamine H, Fukuhara Y, Kuno T. Concentration of mRNA for von Willebrand factor in platelets of type I von Willebrand disease. Clin Chim Acta 1996; 245 (1) 125-127
• 57 Maroney SA, Haberichter SL, Friese P , et al. Active tissue factor pathway inhibitor is expressed on the surface of coated platelets. Blood 2007; 109 (5) 1931-1937
• 58 Reitsma PH, Ploos van Amstel HK, Bertina RM. Three novel mutations in five unrelated subjects with hereditary protein S deficiency type I. J Clin Invest 1994; 93 (2) 486-492
• 59 Martincic D, Kravtsov V, Gailani D. Factor XI messenger RNA in human platelets. Blood 1999; 94 (10) 3397-3404
• 60 Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 2002; 22 (9) 1381-1389
• 61 Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost 2005; 3 (10) 2185-2192
• 62 Heemskerk JW, Mattheij NJ, Cosemans JM. Platelet-based coagulation: different populations, different functions. J Thromb Haemost 2013; 11 (1) 2-16
• 63 van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 2008; 9 (2) 112-124
• 64 Lhermusier T, Chap H, Payrastre B. Platelet membrane phospholipid asymmetry: from the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J Thromb Haemost 2011; 9 (10) 1883-1891
• 65 Zwaal RF, Comfurius P, van Deenen LL. Membrane asymmetry and blood coagulation. Nature 1977; 268 (5618) 358-360
• 66 Suzuki J, Umeda M, Sims PJ, Nagata S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 2010; 468 (7325) 834-838
• 67 Bevers EM, Comfurius P, van Rijn JL, Hemker HC, Zwaal RF. Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 1982; 122 (2) 429-436
• 68 Bevers EM, Comfurius P, Zwaal RF. Changes in membrane phospholipid distribution during platelet activation. Biochim Biophys Acta 1983; 736 (1) 57-66
• 69 Dachary-Prigent J, Freyssinet JM, Pasquet JM, Carron JC, Nurden AT. Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups. Blood 1993; 81 (10) 2554-2565
• 70 London FS, Marcinkiewicz M, Walsh PN. A subpopulation of platelets responds to thrombin- or SFLLRN-stimulation with binding sites for factor IXa. J Biol Chem 2004; 279 (19) 19854-19859
• 71 Wolfs JL, Comfurius P, Rasmussen JT , et al. Activated scramblase and inhibited aminophospholipid translocase cause phosphatidylserine exposure in a distinct platelet fraction. Cell Mol Life Sci 2005; 62 (13) 1514-1525
• 72 Kalafatis M, Egan JO, van 't Veer C, Cawthern KM, Mann KG. The regulation of clotting factors. Crit Rev Eukaryot Gene Expr 1997; 7 (3) 241-280
• 73 Bouchard BA, Williams JL, Meisler NT, Long MW, Tracy PB. Endocytosis of plasma-derived factor V by megakaryocytes occurs via a clathrin-dependent, specific membrane binding event. J Thromb Haemost 2005; 3 (3) 541-551
• 74 Gould WR, Simioni P, Silveira JR, Tormene D, Kalafatis M, Tracy PB. Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor. J Thromb Haemost 2005; 3 (3) 450-456
• 75 Weiss HJ, Lages B, Zheng S, Hayward CP. Platelet factor V New York: a defect in factor V distinct from that in factor V Quebec resulting in impaired prothrombinase generation. Am J Hematol 2001; 66 (2) 130-139
• 76 Fager AM, Wood JP, Bouchard BA, Feng P, Tracy PB. Properties of procoagulant platelets: defining and characterizing the subpopulation binding a functional prothrombinase. Arterioscler Thromb Vasc Biol 2010; 30 (12) 2400-2407
• 77 Stalker TJ, Traxler EA, Wu J , et al. Hierarchical organization in the hemostatic response and its relationship to the platelet-signaling network. Blood 2013; 121 (10) 1875-1885
• 78 Jorgensen L, Rowsell HC, Hovig T, Mustard JF. Resolution and organization of platelet-rich mural thrombi in carotid arteries of swine. Am J Pathol 1967; 51 (5) 681-719
• 79 Stehbens WE, Biscoe TJ. The ultrastructure of early platelet aggregation in vivo. Am J Pathol 1967; 50 (2) 219-243
• 80 White JG. Platelet structural physiology: the ultrastructure of adhesion, secretion, and aggregation in arterial thrombosis. Cardiovasc Clin 1987; 18 (1) 13-33
• 81 Palmerini T, Tomasi L, Barozzi C , et al. Detection of tissue factor antigen and coagulation activity in coronary artery thrombi isolated from patients with ST-segment elevation acute myocardial infarction. PLoS ONE 2013; 8 (12) e81501
• 82 Hernández Vera R, Vilahur G, Ferrer-Lorente R, Peña E, Badimon L. Platelets derived from the bone marrow of diabetic animals show dysregulated endoplasmic reticulum stress proteins that contribute to increased thrombosis. Arterioscler Thromb Vasc Biol 2012; 32 (9) 2141-2148
• 83 Tyagi T, Ahmad S, Gupta N , et al. Altered expression of platelet proteins and calpain activity mediate hypoxia-induced prothrombotic phenotype. Blood 2014; 123 (8) 1250-1260
• 84 Karges HE, Funk KA, Ronneberger H. Activity of coagulation and fibrinolysis parameters in animals. Arzneimittelforschung 1994; 44 (6) 793-797
• 85 Windberger U, Bartholovitsch A, Plasenzotti R, Korak KJ, Heinze G. Whole blood viscosity, plasma viscosity and erythrocyte aggregation in nine mammalian species: reference values and comparison of data. Exp Physiol 2003; 88 (3) 431-440
• 86 Basavaraj MG, Olsen JO, Østerud B, Hansen JB. Differential ability of tissue factor antibody clones on detection of tissue factor in blood cells and microparticles. Thromb Res 2012; 130 (3) 538-546
• 87 Jayachandran M, Sanzo A, Owen WG, Miller VM. Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in platelets. Am J Physiol Heart Circ Physiol 2005; 289 (5) H1908-H1916
• 88 Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev 2009; 23 (5) 225-229
• 89 Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13 (1) 34-45