Summary
We have investigated the ability of serum from uremic patients to modify the thrombogenic
properties of the endothelium. The effects of uremic medium on the morphology of endothelial
cells (ECs), and their resistance to flow was analyzed. The influence of uremic media
on the reactivity of the extracellular matrix (ECM) generated by ECs towards normal
platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to
uremic medium resulted in abnormal cell morphology and signs of an accelerated growth.
Detachment of ECs exposed to circulating blood was increased when cells had been grown
with media supplemented with uremic serum (21% vs. 14% non exposed). Platelet deposition
was significantly elevated on ECMs generated in the presence of uremic media (uremicECMs)
(p<0.01 vs. control studies). Effects of uremic serum were not observed at short incubation
periods (5 h) but were evident after 24 or 72 h of incubation. Northern blot analysis
revealed increased expression of tissue factor (TF) mRNA in ECs exposed to uremic
conditions. Immunocytochemical methods detected an augmented expression of TF antigen
on uremic ECMs. Incubation of ECMs with an antibody to human tissue factor prevented
the increase in platelet deposition observed in uremic ECMs, suggesting that the presence
of TF in ECM could be responsible for the enhanced platelet deposition. Results from
our study indicate that uremic medium impairs the antithrombotic functions of cultured
endothelial cells.
Keywords
Uremia - endothelial cells - tissue factor - hemostatic balance - atherothrombosis