Background: Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of coronary artery disease (CAD). Tissue factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key in triggering thrombin generation. The aim of this study was to assess the levels of TF and tissue factor pathway inhibitor (TFPI) in patients with angiographically documented CAD and also to evaluate TF induction on monocytes in vitro in the presence of these plasmas from patients with CAD. Methods: Plasma antigen levels of soluble TF and TFPI were measured in 65 CAD patients and 22 healthy controls. Surface TF expression on monocytes from a healthy donor treated with plasma samples was evaluated by flow cytometry with a direct double-color immunofluorescence technique. Results: Significantly elevated levels of both TF and TFPI were found in CAD patients compared with healthy controls (303.6 ± 134.1 vs. 187.3 ± 108.7 pg/ml, p < 0.05; 85.2 ± 48.6 vs. 65.0 ± 29.0 ng/ml, p < 0.05). By flow cytometry, monocytes from a healthy donor displayed higher TF antigen expression when incubated in the presence of CAD plasmas than in control plasmas (34.6 ± 10.7 vs. 23.2 ± 10.2%, p < 0.05). Conclusions: The high levels of circulating TF are present in CAD, which were not sufficiently inhibited by the elevated TFPI plasma levels. Although the source of circulating TF is unclear, TF induction of monocytes by plasma from CAD patients may contribute to the hypercoagulable state.

1.
Carson SD, Brozna JP: The role of tissue factor in the production of thrombin. Blood Coagul Fibrinolysis 1993;4:281–292.
2.
Nemerson Y: Tissue factor and hemostasis. Blood 1988;71:1–8.
3.
Edington TS, Mackman N, Ruf W: The structural biology of expression and function of tissue factor. Thromb Haemost 1991;66:67–79.
4.
Drake TA, Morrissey JH, Edgington TS: Selective cellular expression of tissue factor in human tissues. Am J Pathol 1989;134:1087–1097.
5.
McGee M, Li L: Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages. J Biol Chem 1991;266:8079–8085.
6.
Camerer E, Kolsto AB, Prydz H: Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res 1996;81:1–41.
7.
Rotherberger H, Zimmerman TS, Spiegelberg HC, Vaughan JH: Leukocyte procoagulant activity: Enhancement of production in vitro by IgG and antigen-antibody complexes. J Clin Invest 1977;59:549–557.
8.
Bartha K, Brisson C, Archipoff G, de la Salle C, Lanza F, Cazenave JP, Beretz A: Thrombin regulates tissue factor and thrombomodulin mRNA levels and activities in human saphenous vein endothelial cells by distinct mechanisms. J Biol Chem 1993;268:421–429.
9.
Broze GJ: Tissue factor pathway inhibitor. Thromb Haemost 1995;74:90–93.
10.
Novotny WF, Brown SG, Girard TJ, Miletich JP, Brose GJ: Platelets secrete a coagulation inhibitor functionally and antigenically similar to the lipoprotein associated coagulation inhibitor. Blood 1988;72:2020–2025.
11.
Kazma Y: The importance of the binding of factor Xa to phospholipids in the inhibitory mechanism of tissue factor pathway inhibitor: The transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory action of tissue factor pathway inhibitor. Thromb Haemost 1997;77:492–497.
12.
Sandset PM, Warn-Cramer BJ, Maki SL, Rapaport SI: Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. Blood 1991;78:1496–1502.
13.
Bregengard C, Nordfang O, Wildgoose P, Svendsen O, Hedner U, Diness V: The effect two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits. Blood Coagul Fibrinolysis 1993;4:699–706.
14.
Neri Serneri GG, Gensini GF, Abbate R, Laureano R, Parodi O: Is raised plasma fibrinopeptide A a marker of acute coronary insufficiency? Lancet 1980;ii:982–983.
15.
Gallino A, Haeberli A, Bauer HR, Straub PW: Fibrin formation and platelet aggregation in patients with severe coronary artery disease: Relationship with the degree of myocardial ischemia. Circulation 1985;72:27–30.
16.
Theroux P, Latour JG, Leger-Gauthier C, De Lara J: Fibrinopeptide A and platelet factor 4 levels in unstable angina. Circulation 1987;75:156–162.
17.
Neri Serneri GG, Abbate R, Gori A, Attanasio M, Martini F, Giusti B, Dabizzi P, Poggesi L, Modesti PA, Trotta F, Rostagno C, Boddi M, Gensini GF: Transient intermittent lymphocyte activation is responsible for the instability of unstable angina. Circulation 1992;86:790–797.
18.
Freeburn JC, Wallace JMW, Strain JJ, Sinnamon DG, Craig BM, Johnson D, Gilmore WS: Monocyte tissue factor-like activity in post myocardial infarction patients. Br J Haematol 1998;102:605–608.
19.
Leatham EW, Bath PM, Tooze JA, Camm AJ: Increased monocyte tissue factor expression in coronary disease. Br Heart J 1995;73:10–13.
20.
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;134:253–259.
21.
Misumi K, Ogawa H, Yasue H, Soejima H, Suefuji H, Nishiyama K, Takazoe K, Kugiyama K, Tsuji I, Kumeda K, Nakamura S: Comparison of plasma tissue factor levels in unstable and stable angina pectoris. Am J Cardiol 1998;81:22–26.
22.
Braunwald E: Unstable angina: A classification. Circulation 1989;80:410–414.
23.
Albrecht S, Kotzsch M, Siegert G, Luther T, Grobmann H, Grober M, Muller M: Detection of circulating tissue factor and factor VII in a normal population. Thromb Haemost 1996;75:772–777.
24.
Wada H, Nakase T, Nakaya R, Minamikawa K, Wakita Y, Kaneko T, Ohiwa M, Deguchi K, Shirakawa S: Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. Am J Hematol 1994;45:232–236.
25.
Koyama T, Nishida K, Ohdama S, Sawada M, Murakami N, Hirosawa S, Kuriyama R, Matsuzawa K, Hasegawa R, Aoki N: Determination of plasma tissue factor antigen and its clinical significance. Br J Haematol 1994;87:343–347.
26.
Sandset PM, Sirnes PA, Abildgaard U: Factor VII and extrinsic pathway inhibitor in acute coronary disease. Br J Haematol 1989;72:391–396.
27.
Moor E, Silveira A, van’t Hooft F, Suontaka AM, Eriksson P, Blomback M, Hamsten A: Coagulation factor VII mass and activity in young men with myocardial infarction at a young age. Arterioscler Thromb Vasc Biol 1995;15:655–664.
28.
Marmur JD, Rossikhina M, Guha A, Fyfe B, Friedrich V, Mendlowiz M, Nemerson Y, Taubman MB: Tissue factor is rapidly induced in arterial smooth muscle after balloon injury. J Clin Invest 1993;91:2253–2259.
29.
Gregory SA, Morrissey JH, Edgington TS: Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989;9:2752–2755.
30.
Tremoli E, Camera M, Toschi V, Colli S: Tissue factor in atherosclerosis. Atherosclerosis 1999;144:273–283.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.