Dipyridamole induces changes in the thrombogenic properties of extracellular matrix generated by endothelial cells in culture

Abstract

Dipyridamole (DIP) is a drug widely used as an antiplatelet agent, which also has effects on endothelial cells. In this study, the effects of treating confluent endothelial cell monolayers (EC) with DIP on EC viability (trypan blue exclusion test) and metabolic activity (3H-thymidine incorporation) were examined. Platelet reactivity of the extracellular matrix (ECM) produced by untreated and DIP-treated ECs was determined morphometrically by a perfusion technique. Levels of ECM-associated von Willebrand factor (vWF) and fibronectin (FN) were also quantified (ELISA). The present results indicate that treatment of EC with 10 microM DIP did not reduce EC viability but that the incorporation of labelled nucleotides was significantly decreased (p less than 0.01). Platelet deposition onto the ECM generated by DIP-treated cells, perfused at a shear rate of 1300 sec-1, differed significantly with respect to controls (p less than 0.05), and platelet adhesion was also reduced (25% less, p less than 0.05). This effect was shear rate dependent, as no differences were noted when the ECMs were perfused at 300 sec-1 shear rate. Levels of VWF and FN associated with ECM remained unchanged with respect to controls. These results suggest that treatment with DIP alters EC metabolic activity, which in turn, influences the reactivity of the ECM generated by treated cells.