Systemic endothelial cell markers in primary antiphospholipid syndrome.
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.
Williams
F M
FM
Department of Haematology and Lupus Research, St Thomas' Hospital, London, UK.
Parmar
K
K
Hughes
G R
GR
Hunt
B J
BJ
D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism*; D015539:Platelet Activation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors; D008222:Lymphokines; D019007:P-Selectin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors