DIPYRIDAMOLE INDUCES CHANGES IN THE THROMBOGENIC PROPERTIES OF ENDOTHELIAL-CELL EXTRACELLULAR MATRICES

Dipyridamole (DIP) is a pirydo-pirymidine drug widely used as an antiplatelet agent.DIP has also been demonstrated to have effects on various cultured cells. We studied platelet reactivity of extracellular matrices (ECMs) produced by untreated (ECM-c) and DIP-treated (ECM-DIP) endothelial cells (ECs).Confluent monolayers of EC were incubated in buffer containing 0 or 10 pM. DIP for 48 h. The ECMs were prepared by removing the EC with 2% EGTA (1 h at 37°C). Platelet deposition onto the ECMs was measured under flow conditions using a flat chamber perfusion model ECM-c and ECM-DIP were exposed for 5 min to whole blood at shear rates of 300 or 1300 sec~1.Then, the perfused ECMs were processed for cross sectional morphometric evaluation using a computer system. The platelet, deposition is expressed as total surface covered with platelets (mean±SEM ) and shown in the table.Platelet aggregate formation on ECM-DIP at 1300 sec-1 was also reduced(by 25%)as measured morphometrically. We conclude that DIP-treatment of EC results in ECM modifications,which in turn decrease ECM-platelet interactions.These data also suggest that pharmacological treatment of the endothelium influences basement membrane reactivity.