Intimal Tissue Factor Activity Is Released from the Arterial Wall after Injury

Summary

Tissue factor (TF), the initiator of coagulation, has been implicated as a critical mediator of arterial thrombosis. Previous studies have demonstrated that TF is rapidly induced in the normal rodent arterial wall by balloon injury, but is not associated with fibrin deposition. A second injury, however, performed 10–14 days after the first, is followed by small platelet-fibrin microthrombi. This study was undertaken to better localize active TF in balloon-injured rat arteries and to explore possible mechanisms underlying the apparent discrepancy between injury-induced TF expression and the lack of large platelet-fibrin thrombi. By immunohistochemistry, TF antigen was first detected in the media 24 h after injury to rat aortas, and subsequently accumulated in the neointima. Using an ex vivo flow chamber, no TF activity (Factor Xa generation) was found on the luminal surface of normal or injured aortas. Wiping the luminal surface with a cotton swab exposed TF activity in all vessels; levels were increased ≈3-fold in arteries containing a neointima. The exposed TF activity was rapidly washed into the perfusate, rendering the luminal surface inactive. The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury.

Keywords

Vascular smooth muscle - thrombosis - arterial injury - tissue factor

^* Current address: Dr. P. L. A. Giesen, Synapse BV, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands

^** Current address: Dr. B. S. Fyfe, Department of Pathology and Laboratory Medicine, Medical College of Pennsylvania and Hahnemann University, Philadelphia, PA, USA

• References

• 1 Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell 1986; 46: 155-69.
• 2 Schwartz SM, Heimark RL, Majesky MW. Developmental mechanisms underlying pathology of arteries. Physiol Rev 1990; 70: 1177-209.
• 3 McNamara CA, Sarembock IJ, Bachhuber BG, Stouffer GA, Ragosta M, Barry W, Gimple LW, Powers ER, Owens GK. Thrombin and vascular smooth muscle cell proliferation: implications for atherosclerosis and restenosis. Semin Thromb Hemost 1996; 22: 139-44.
• 4 Fager G. Thrombin and proliferation of vascular smooth muscle cells. Circ Res 1995; 77: 645-50.
• 5 Coughlin SR. Molecular mechanisms of thrombin signaling. Semin Hematol 1994; 31: 270-7.
• 6 Huang CL, Ives HE. Growth inhibition by protein kinase C late in mitogenesis. Nature 1987; 329: 849-50.
• 7 Bar-Shavit R, Benezra M, Eldor A, Hy-Am E, Fenton JWd, Wilner GD, Vlodavsky I. Thrombin immobilized to extracellular matrix is a potent mitogen for vascular smooth muscle cells: nonenzymatic mode of action [published erratum appears in Cell Regul 1990 Oct; 1 (11): 873]. Cell Regulation 1990; 01: 453-63.
• 8 Ko FN, Yang YC, Huang SC, Ou JT. Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat. J Clin Invest 1996; 98: 1493-501.
• 9 Gasic GP, Arenas CP, Gasic TB, Gasic GJ. Coagulation factors X, Xa, and protein S as potent mitogens of cultured aortic smooth muscle cells. Proceedings of the National Academy of Sciences of the United States of America 1992; 89: 2317-20.
• 10 Edgington TS, Mackman N, Brand K, Ruf W. The structural biology of expression and function of tissue factor. Thromb Haemost 1991; 66: 67-79.
• 11 Nemerson Y. Tissue factor and the initiation of blood coagulation. Advances in Experimental Medicine and Biology 1987; 214: 83-94.
• 12 Nemerson Y. Tissue factor: then and now. Thromb Haemos 1995; 74: 180-4.
• 13 Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, Chiariello M, Bach R, Garen A, Konigsberg WK. etal A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circulation Research 1994; 74: 56-63.
• 14 Jang IK, Gold HK, Leinbach RC, Fallon JT, Collen D, Wilcox JN. Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis. Arterioscler Thromb 1992; 12: 948-54.
• 15 Jang Y, Guzman LA, Lincoff AM, Gottsauner-Wolf M, Forudi F, Hart CE, Courtman DW, Ezban M, Ellis SG, Topol EJ. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. Circulation 1995; 92: 3041-50.
• 16 Golino P, Ragni M, Cirillo P, D’Andrea D, Scognamiglio A, Ravera A, Buono C, Ezban M, Corcione N, Vigorito F, Condorelli M, Chiariello M. Antithrombotic effects of recombinant human, active site-blocked factor VIIa in a rabbit model of recurrent arterial thrombosis. Circ Res 1998; 82: 39-46.
• 17 Harker LA, Hanson SR, Wilcox JN, Kelly AB. Antithrombotic and antilesion benefits without hemorrhagic risks by inhibiting tissue factor pathway. Haemost 1996; 26 (Suppl. 01) 76-82.
• 18 Oltrona L, Speidel CM, Recchia D, Wickline SA, Eisenberg PR, Abendschein DR. Inhibition of tissue factor-mediated coagulation markedly attenuates stenosis after balloon-induced arterial injury in minipigs. Circulation 1997; 96: 646-52.
• 19 Taubman MB, Marmur JD, Rosenfield CL, Guha A, Nichtberger S, Nemerson Y. Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells. Role of Ca²⁺ mobilization and protein kinase C activation. J Clin Invest 1993; 91: 547-52.
• 20 Schecter AD, Giesen PL, Taby O, Rosenfield CL, Rossikhina M, Fyfe BS, Kohtz DS, Fallon JT, Nemerson Y, Taubman MB. Tissue factor expression in human arterial smooth muscle cells. TF is present in three cellular pools after growth factor stimulation. J Clin Invest 1997; 100: 2276-85.
• 21 Schecter AD, Rollins BJ, Zhang YJ, Charo IF, Fallon JT, Rossikhina M, Giesen PL, Nemerson Y, Taubman MB. Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997; 272: 28568-73.
• 22 Marmur JD, Thiruvikraman SV, Fyfe BS, Guha A, Sharma SK, Ambrose JA, Fallon JT, Nemerson Y, Taubman MB. Identification of active tissue factor in human coronary atheroma. Circulation 1996; 94: 1226-32.
• 23 Speidel CM, Eisenberg PR, Ruf W, Edgington TS, Abendschein DR. Tissue factor mediates prolonged procoagulant activity on the luminal surface of balloon-injured aortas in rabbits. Circulation 1995; 92: 3323-30.
• 24 Speidel CM, Thornton JD, Meng YY, Eisenberg PR, Edgington TS, Abendschein DR. Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa. Coronary Artery Disease 1996; 07: 57-62.
• 25 Gallo R, Fallon JT, Toschi V, Gertz SD, Padurean A, Nemerson Y, Chesebro J, Fuster V, Badimon JJ. Bi-phasic increase of tissue factor activity after angioplasty in porcine coronary arteries. Circulation 1995; 92: I-354 (Abstract).
• 26 Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Laboratory Investigation 1983; 49: 327-33.
• 27 Groves HM, Kinlough-Rathbone RL, Richardson M, Jorgensen L, Moore S, Mustard JF. Thrombin generation and fibrin formation following injury to rabbit neointima. Studies of vessel wall reactivity and platelet survival. Laboratory Investigation 1982; 46: 605-12.
• 28 Richardson M, Kinlough-Rathbone RL, Groves HM, Jorgensen L, Mustard JF, Moore S. Ultrastructural changes in re-endothelialized and non-endothelialized rabbit aortic neo-intima following re-injury with a balloon catheter. Br J Exp Pathol 1984; 65: 597-611.
• 29 Stemerman BM. Thrombogenesis of the rabbit arterial plaque. Am. J Pathol 1973; 73: 7-26.
• 30 Asada Y, Hara S, Tsuneyoshi A, Hatakeyama K, Kisanuki A, Marutsuka K, Sato Y, Kamikubo Y, Sumiyoshi A. Fibrin-rich and platelet-rich thrombus formation on neointima: recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta. Thromb Haemost 1998; 80: 506-11.
• 31 Courtman DW, Schwartz SM, Hart CE. Sequential injury of the rabbit abdominal aorta induces intramural coagulation and luminal narrowing independent of intimal mass: extrinsic pathway inhibition eliminates luminal narrowing. Circ Res 1998; 82: 996-1006.
• 32 Maynard JR, Heckman CA, Pitlick FA, Nemerson Y. Association of tissue factor activity with the surface of cultured cells. J Clin Invest 1975; 55: 814-24.
• 33 Bach RR, Moldow CF. Mechanism of tissue factor activation on HL-60 cells. Blood 1997; 89: 3270-6.
• 34 Carson SD. Manifestation of cryptic fibroblast tissue factor occurs at detergent concentrations which dissolve the plasma membrane. Blood Coagul Fibrinolysis 1996; 07: 303-13.
• 35 Drake TA, Ruf W, Morrissey JH, Edgington TS. Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. J Cell Biol 1989; 109: 389-95.
• 36 Le DT, Rapaport SI, Rao LV. Relations between factor VIIa binding and expression of factor VIIa/tissue factor catalytic activity on cell surfaces. J Biol Chem 1992; 267: 15447-54.
• 37 Mulder AB, Smit JW, Bom VJ, Blom NR, Ruiters MH, Halie MR, van der Meer J. Association of smooth muscle cell tissue factor with caveolae. Blood 1996; 88: 1306-13.
• 38 Greeno EW, Bach RR, Moldow CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 1996; 75: 281-9.
• 39 Sevinsky RJ, Rao MVL, Ruf W. Ligand-induced protease receptor translocation into caveolae: A mechanism for regulating cell surface proteolsis of the tissue factor-dependent coagulation pathway. J Cell Biol 1996; 133: 293-304.
• 40 Marmur JD, Rossikhina M, Guha A, Fyfe B, Friedrich V, Mendlowitz M, Nemerson Y, Taubman MB. Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. J Clin Invest 1993; 91: 2253-9.
• 41 Chemnitz J, Christensen BC. Repair in arterial tissue 2 years after a severe single dilatation injury: the regenerative capacity of the rabbit aortic wall. The importance of endothelium and of the state of subendothelial connective tissue to reconstitution of the intimal barrier. Virchows Arch A Pathol Anat Histopathol 1991; 418: 523-30.
• 42 Badimon L, Badimon JJ, Galvez A, Chesebro JH, Fuster V. Influence of arterial damage and wall shear rate on platelet deposition. Ex vivo study in a swine model. Arteriosclerosis 1986; 06: 312-20.
• 43 Miletich JP, Broze GJ, Majerus PW. The synthesis of sulfated dextran beads for isolation of human plasma coagulation factors II, IX, and X. Anal Biochem 1980; 105: 304-10.
• 44 Thiruvikraman SV, Guha A, Roboz J, Taubman MB, Nemerson Y, Fallon JT. In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin-labeled factors VIIa and X. Lab Invest 1996; 75: 451-61.
• 45 Groves MH, Rathbone-Kinlough LR, Richardson M, Jorgensen L, Moore S, Mustard FJ. Thrombin generation and fibrin formation following injury to rabbit neointima. Laboratory Invest 1982; 46: 605-12.
• 46 Richardson M, Rathbone-Kinlough LR, Groves MH, Jorgensen LG, Mustard FJ, Moore S. Ultrastructural changes in re-endothelialized and non-endothelialized rabbit aortic neo-intima following re-injury with a balloon catheter. Br J Exp Path 1984; 65.
• 47 Fingerle J, Au YP, Clowes AW, Reidy MA. Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis 1990; 10: 1082-7.
• 48 Broze GJ. Tissue factor pathway inhibitor and the revised theory of coagulation. Annu Re. Med 1995; 46: 103-12.
• 49 Hatakeyama K, Asada Y, Marutsuka K, Sato Y, Kamikubo Y, Sumiyoshi A. Localization and activity of tissue factor in human aortic atherosclerotic lesions. Atherosclerosis 1997; 133: 213-9.
• 50 Suefuji H, Ogawa H, Yasue H, Kaikita K, Soejima H, Motoyama T, Mizuno Y, Oshima S, Saito T, Tsuji I, Kumeda K, Kamikubo Y, Nakamura S. Increased plasma tissue factor levels in acute myocardial infarction. Am Heart J 1997; 134: 253-9.
• 51 Key NS, Slungaard A, Dandelet L, Nelson SC, Moertel C, Styles LA, Kuypers FA, Bach RR. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood 1998; 91: 4216-23.
• 52 Fukuda C, Iijima K, Nakamura K. Measuring tissue factor (factor III) activity in plasma. Clin Chem 1989; 35: 1897-900.
• 53 Giesen PLA, Rauch U, Bohrmann B, Kling D, Himber J, Roque M, Fallon JT, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Blood-borne tissue factor: a new view of thrombosis. Proc Natl Acad Sci US. 1999 in Press.
• 54 Schecter SD, Giesen PLA, Fallon JT, Nemerson Y, Taubman MB. PDGF induces the release of active tissue factor (TF) from smooth muscle cells: a potential source of extracellular TF in the atherosclerotic plaque. Circulation 1997; 96: I-43A.
• 55 Mallat Z, Hugel B, Ohan J, Lesche G, Freyssinet JM, Tedgui A. Shed Membrane Microparticles With Procoagulant Potential in Human Atherosclerotic Plaques: A Role for Apoptosis in Plaque Thrombogenicity. Circulation 1999; 99: 348-53.
• 56 Carson SD, Perry GA, Pirruccello SJ. Fibroblast tissue factor: calcium and ionophore induce shape changes, release of membrane vesicles, and redistribution of tissue factor antigen in addition to increased procoagulant activity. Blood 1994; 84: 526-34.
• 57 Satta N, Freyssinet JM, Toti F. The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide. Br J Haematol 1997; 96: 534-42.
• 58 Taubman MB, Giesen PLA, Schecter AD, Nemerson Y. Regulation of the procoagulant response to arterial injury. Thromb Haemost 1999; 82 (02) 801-5.