Nephrol Dial Transplant (1995) 10: 2199-2204
© 1995 European Renal Association-European Dialysis and Transplant Association
research-article
Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix
1Servicios de Hemoterapia y Hemostasia y, Hospital Clinic Barcelona, Catalonia, Spain 2Servicios de Nefrologia, Hospital Clinic Barcelona, Catalonia, Spain
Correspondence and offprint requests to: Correspondence and offprint requests to: Dr Aleix Cases, Servicio de Nefrologia, Hospital Clinic i Provincial, C/ Villarroel 170, 08036, Barcelona, Spain
Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured ‘ex vivo’ under flow conditions (5 min, wall shear rate 800 s–1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P<0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 ± 1.9% vs 16.7±1.8% in controls, P<0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood.
These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.
Keywords: endothelial cell dysfunction; vascular subendothelium; uraemia; platelets
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