Elevated Tissue Factor and Tissue Factor Pathway Inhibitor Circulating Levels in Ischaemic Heart Disease Patients

Michela Falciani; Anna Maria Gori; Sandra Fedi; Ludia Chiarugi; Ignazio Simonetti; Roberto Piero Dabizzi; Domenico Prisco; Guglielmina Pepe; Rosanna Abbate; Gian Franco Gensini; Gian Gastone Neri Serneri

doi:10.1055/s-0037-1614932

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 79(03): 495-499
DOI: 10.1055/s-0037-1614932

Review Articles

Schattauer GmbH

Elevated Tissue Factor and Tissue Factor Pathway Inhibitor Circulating Levels in Ischaemic Heart Disease Patients

Michela Falciani

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Anna Maria Gori

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Sandra Fedi

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Ludia Chiarugi

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Ignazio Simonetti

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Roberto Piero Dabizzi

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Domenico Prisco

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Guglielmina Pepe

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Rosanna Abbate

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Gian Franco Gensini

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

,

Gian Gastone Neri Serneri

¹From the Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy

› Institutsangaben

Abstract

Summary

Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD.

We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT).

TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml).

Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p <0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p <0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 μg/l; range 1.7-21.0 μg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p <0.001) than those found in control subjects (TAT median 2.3 μg/l; range 1.4-4.2 μg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l).

As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.

Volltext

Referenzen

References
1 Nemerson Y. Tissue Factor: Then and now.. Thromb Haemost 1995; 7: 180-4.
2 Nemerson Y. Tissue factor and haemostasis.. Blood 1988; 71: 1-8.
3 Novotny WF, Brown SG, Girard TJ, Miletich JP, Brose Jr. GJ. Platelets secrete a coagulation inhibitor functionally and antigenically similar to the lipoprotein associated coagulation inhibitor.. Blood 1988; 72: 2020-5.
4 Werling RW, Zacharski LR, Kisiel W, Bajaj SP, Memoli VA, Rosseau SM. Distribution of tissue factor pathway inhibitor in normal and malignant human tissues.. Thromb Haemost 1993; 69: 366-9.
5 Neri Serneri GG, Gensini GF, Abbate R, Laureano R, Parodi O. Is raised plasma fibrinopeptide A a marker of acute coronary insufficiency?. Lancet 1980; 2: 982-3.
6 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.
7 Theroux P, Latour JG, Leger-Gauthier C, De Lara J. Fibrinopeptide A and platelet factor 4 levels in unstable angina.. Circulation 1987; 75: 156-62.
8 Neri Serneri GG, Abbate R, Gori AM, 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 angina.. Circulation 1992; 86: 790-7.
9 Sandset PM, Sirnes PA, Abildgaard U. Factor VII and extrinsic pathway inhibitor in acute coronary disease.. Br J Haematol 1989; 72: 391-6.
10 Neri Serneri GG, Abbate R, Gensini GF, Gori AM, Attansio M, Martini F. Monocyte activation and increased proagulant activity in unstable angina.. Lancet 1990; 336: 1444-5.
11 Soejima H, Ogawa H, Yasue H, Suefuji H, Kaikita K, Tsuji I, Kumeda K, Aoyama N. Effects of enalapril on tissue factor in patients with uncomplicated acute myocardial infarction.. Am J Cardiol 1996; 78: 336-40.
12 Shimura M, Wada H, Wakita Y, Nakase T, Hiyoyama K, Nagaya A, Mori Y, Shiku H. Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation.. Am J Hematol 1996; 52: 165-70.
13 Sandset PM, Warn-Cramer BJ, Rao LVM, Maki SL, Rapaport SI. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant.. Proc Natl Acad Sci USA 1991; 88: 708-12.
14 Calmus Y, Robert A. Increase in monocyte procoagulant activity with age.. Thromb Res 1986; 41: 133-6.
15 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans.. J Clin Invest 1987; 80: 1527-34.
16 Cadroy Y, Pierrejean D, Fontan B, Sie P, Boneau B. Influence of aging on the activity of the hemostatic system: prothrombin fragment 1+2, thrombinantithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years.. Nouv Rev Fr Haematol 1992; 34: 43-6.
17 Taubman MB. Tissue factor regulation in vascular smooth muscle: a summary of studies performed using in vivo and in vitro models.. Am J Cardiol 1993; 72: 55C-60C.
18 Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernadez-Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.. Circulation 1997; 95: 594-9.
19 Moreno PR, Bernardi VH, Lopez-Cuellar J, Murcia AM, Palacios IF, Gold HK, Mehran R, Sharma SK, Nemerson Y, Fuster V, Fallon JT. Macrophages, smooth muscle cells, and tissue factor in unstable angina. implications for cell-mediated thrombogenicity in acute coronary syndromes.. Circulation 1996; 94: 3090-7.
20 Lorenzet R, Niemetz J, Marcus AJ, Broekman MJ. Enhancement of mono-nuclear procoagulant activity by platelet 12-Hydroxyeicosatetraenoic acid.. J Clin Invest 1986; 78: 418-23.
21 Celi A, Pellegrini G, Lorenzet R, De Blasi A, Ready N, Furie BC, Furie B. P-selectin induces the expression of tissue factor on monocytes.. Proc Natl Acad Sci USA 1994; 91: 8767-71.
22 Ernofsson M, Siegbahn A. Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor.. Thromb Res 1996; 83: 307-20.
23 Vaddi K, Nicolini FA, Mehta P, Mehta JL. Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease.. Circulation 1994; 90: 694-9.
24 Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone MA. Inter-leukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.. J Exp Med 1984; 160: 618-23.
25 Nawroth PP, Handley DA, Esmon CT, Stern DM. Interleukin 1 induces endothelial cells procoagulant while suppressing cell-surface anticoagulant activity.. Proc Natl Acad Sci USA 1986; 83: 3460-4.
26 Conkling PR, Greenberg CS, Weinberg JB. Tumor Necrosis Factor induces Tissue factor-like activity in human leukemia cell line U 937 and peripheral blood monocytes.. Blood 1988; 72: 128-33.
27 Carlsen E, Flatmark A, Prydz H. Cytokine-induced procoagulant activity in monocytes and endothelial cells. Further enhancement by ciclosporine.. Transplantation 1988; 46: 575-80.
28 Del Prete GF, De Carli M, Lammel RM, D’Elios MM, Daniel KC, Giusti B, Abbate R, Romagnani S. Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes.. Blood 1995; 86: 250-7.
29 Ameri A, Kuppuswamy MN, Basu S, Bajaj SP. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators.. Blood 1992; 71: 259-62.
30 Osterud B, Bajaj MS, Bajaj SP. Sites of tissue factor pathway inhibitor (TFPI) and tissue factor expression under physiologic and pathologic conditions.. Thromb Haemost 1995; 73: 873-5.
31 Warshawsky I, Bu G, Mast A, Saffitz JE, Broze Jr GJ, Schwartz AL. The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo.. J Clin Invest 1995; 95: 1773-81.
32 Farah B, Vuillemenot A, Lecompte T, Bara L, Pasquier C, Jebara V, Carpentier A, Fabiani JN. Myocardial neutrophil sequestration and activation related to the reperfusion of human heart during coronary artery surgery.. Cardiovasc Res 1994; 28: 1226-30.
33 Dinerman JL, Metha JL. Endothelial, platelet and leukocyte interactions in ischemic heart disease: insights into potential mechanisms and their clinical relevance.. J Am Coll Cardiol 1990; 16: 207-22.
34 Ikeda H, Nakayama H, Oda T, Kuwano K, Yamaga A, Ueno T, Yoh M, Hiyamuta K, Koga Y, Toshima H. Neutrophil activation after percutaneous transluminal coronary angioplasty.. Am Heart J 1994; 128: 1091-8.
35 Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in active coronary disease.. Am J Cardiol 1990; 65: 168-72.
36 Abumiya T, Yamaguchi T, Terasaki T, Kokawa T, Kario K, Kato H. Decreased plasma tissue factor pathway inhibitor activity in ischemic stroke patients.. Thromb Haemost 1995; 74: 1050-4.
37 McGee MP, Foster S, Wang X. Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation.. J Exp Med 1994; 179: 1847-54.
38 Willerson JT, Golino P, Eidt J, Campbell WB, Buja M. Specific platelet mediators and unstable coronary artery lesions: experimental evidence and potential clinical implications.. Circulation 1989; 80: 198-205.
39 Pepe G, Giusti B, Attanasio M, Gori AM, Comeglio P, Martini F, Gensini GF, Abbate R, Neri Serneri GG. Tissue factor and plasminogen activator inhibitor type 2 expression in human stimulated monocytes is inhibited by heparin. G.. Pepe, Seminars in Thrombosis and Hemostasis 1997; 23: 135-41.
40 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic pathway inhibitor (EPI).. Throm Res 1988; 50: 803-13.