RSS-Feed abonnieren
DOI: 10.1055/s-0037-1614108
Systemic Endothelial Cell Markers in Primary Antiphospholipid Syndrome
K. Parmar is funded by the Special Trustees of St Thomas’ Hospital.Publikationsverlauf
Received
28. Februar 2000
Accepted after resubmission
24. Juli 2000
Publikationsdatum:
13. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200005/lookinside/thumbnails/10-1055-s-0037-1614108-1.jpg)
Summary
The pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.
* F. M. K. Williams is an ARC Clinical Research Fellow.
-
References
- 1 Blank M, Cohen J, Toder V, Schoenfeld Y. Induction of antiphospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anticardiolipin antibodies. Proc Natl Acad Sci USA 1991; 88: 3069-73.
- 2 Greaves M. Antiphospholipid antibodies and thrombosis. Lancet 1999; 353: 1348-53.
- 3 Hunt BJ, Jurd KM. Endothelial cell activation. BMJ 1998; 316 (7141): 1328-9.
- 4 Achan V, Jurd KM, Hunt BJ. Haemostasis and the systemic inflammatory response. British Journal of Intensive Care 1996; 223-30.
- 5 Del Papa N, Guidali L, Sala A, Buccellati C, Khamashta MA, Ichikawa K, Tinani A, Balestrieri G, Meroni PL. Endothelial cells as target for antiphospholipid antibodies. Arthritis Rheum 1997; 40 (03) 551-61.
- 6 Simantov R, LaSala JM, Lo SK, Gharavi AE, Sammaritano LR, Salmon JE, Silverstein RL. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest 1995; 96: 2211-9.
- 7 Pierangeli SS, Colden-Stanfield M, Liu X, Barker JH, Anderson GL, Harris EN. Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation 1999; 99: 1997-2002.
- 8 Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt A-M, Stern DM. Endothelial cells in physiology and pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
- 9 Amengual O, Atsumi T, Khamashta MA, Hughes GRV. The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 1998; 79: 279-81.
- 10 Cuadrado MJ, Lopez-Pedrera C, Khamashta MA, Camps MT, Tinahones F, Torres A, Hughes GR, Velasco F. Thrombosis in primary antiphospholipid syndrome. Arthritis Rheum 1997; 40 (05) 834-41.
- 11 Williams FMK, Jurd K, Hughes GRV, Hunt BJ. Antiphospholipid syndrome patients’ monocytes are ‘primed’ to express tissue factor. Thromb Haemost 1998; 80: 864-5.
- 12 Dobado-Berrios PM, Lopez-Pedrera C, Velasco F, Aguirre MA, Torres A, Cuadrado MJ. Increased levels of tissue factor mRNA in mononuclear blood cells of patients with primary antiphospholipid syndrome. Thromb Haemost 1999; 82: 1578-82.
- 13 Koyama T, Ohdama S, Aoki N. Plasma tissue factor reflects endothelial cell injury rather than upregulation of tissue factor expression. Thromb Haemost 1997; 78: 972.
- 14 Mechtcheriakova D, Wlachos AHH, Binder BR, Hofer E. Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1. Blood 1999; 93 (11) 3811-23.
- 15 Mrowka C, Sieberth HG. Circulating adhesion molecules ICAM-1, VCAM-1 and E-selectin in systemic vasculitis: marked difference between Wegener’s granulomatosis and systemic lupus erythematosus. Clin Investig 1994; 72 (10) 762-8.
- 16 Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette J-C, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 1999; 42 (07) 1309-11.
- 17 Harris EN, Gharavi AE, Boey ML. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 02 (8361): 1211-4.
- 18 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995; 74: 1185-90.
- 19 Thiagarajan P, Pengo V, Shapiro S. The use of the dilute Russell viper venom time for the daignosis of lupus anticoagulants. Blood 1986; 68: 869-84.
- 20 Rooney AM, McNally T, Mackie IJ, Machin SJ. The Taipan snake venom time: a new test for lupus anticoagulant. J Clin Pathol 1994; 47 (06) 497-501.
- 21 Short PE, Williams CE, Picken AM, Hill FG. Factor VIII related antigen: an improved enzyme immunoassay. Med Lab Sci 1982; 39 (04) 351-5.
- 22 Lakasing L, Campa JS, Parmar K, Poston R, Hunt BJ, Poston L. Normal expression of cell adhesion molecules in placentae from women with systemic lupus erythematosus and the antiphospholipid syndrome. Placenta 2000; 21: 142-9.
- 23 Jurd KM, Stephens CJM, Black MM, Hunt BJ. Endothelial cell activation in cutaneous vasculitis. Clin Exp Dermatol 1996; 21: 28-32.
- 24 Mulvihill N, Foley JB, Ghaisas N, Murphy R, Crean P, Walsh M. Early temporal expression of soluble cellular adhesion molecules in patients with unstable angina and subendocardial myocardial infarction. Am J Cardiol 1999; 83 (08) 1265-7.
- 25 Baldwin AS. The NFkB and IkB proteins: new discoveries and insights. Ann Rev Immunol 1996; 14: 649-81.
- 26 Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. New Engl J Med 1995; 332: 993-7.
- 27 Joseph JE, Donohoe S, Harrison P, Mackie IJ, Machin SJ. Platelet activation and turnover in the primary antiphospholipid syndrome. Lupus 1998; 07: 333-40.
- 28 Lellouche F, Martinuzzo M, Said P, Madouf J, Carreras LO. Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant. Blood 1991; 78: 2894-9.
- 29 Martinuzzo ME, Maclouf J, Carreras LO, Levy-Toledano S. Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation. Thromb Haemost 1993; 70: 667-71.
- 30 Arvieux J, Roussel B, Pouzol P, Colomb MG. Platelet activating properties of murine monoclonal antbodies to beta 2-glycoprotein I. Thromb Haemost 1993; 70: 336-41.
- 31 Atsumi T, Khamashta MA, Haworth RS, Brooks G, Amengual O, Ichikawa K, Koike T. Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1. Arthritis Rheum 1998; 41 (05) 800-7.
- 32 Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D. Vascular permeablility factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535-45.
- 33 Westerman EM, Miles JM, Backonja M, Sundstrom WR. Neuropathologic findings in multi-infarct dementia associated with anticardiolipin antibody. Arthritis Rheum 1992; 35 (09) 1038-41.
- 34 Asherson RA, Derksen RHWM, Harris EN, Bingley PJ, Hoffbrand BI, Gharavi AE, Kater L, Hughes GR. Large vessel occlusion and gangrene in systemic lupus erythematosus and ‘lupus-like’ disease. A report of six cases. J Rheumatol 1986; 13: 740-7.
- 35 Leung DW, Cachianes G, Kuang W-J, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246: 1306-9.