Near-field amplification of antithrombotic effects of dipyridamole through vessel wall cells

Many studies have demonstrated that dipyridamole is not purely an antiplatelet agent but also exerts its antithrombotic properties through the vessel wall. Using a laboratory model in which bovine endothelial cells are seeded to form a subendothelial matrix (SEM), investigators have shown that dipyridamole enhances the antithrombotic action of the endothelium, probably by increasing intracellular levels of cAMP and cGMP through phosphodiesterase inhibition. If so, the antithrombotic action of dipyridamole should also be observable away from the endothelium itself, i.e., a near-field effect. To test this hypothesis, we reseeded the SEM with a monolayer of human umbilical vein endothelial cells (hUVECs), occluding a portion of the SEM with teflon stops. We then treated the SEM with and without hUVECs with various doses of dipyridamole and exposed them to whole blood under flow conditions. Human endothelial cells cultured on the SEM increased its ability to reduce thrombus formation in the adjacent SEM. Dipyridamole enhanced this antithrombotic effect of hUVECs in a dose-dependent manner. No increment in antithrombotic effect was seen in dipyridamole-treated SEM without hUVECs. We therefore conclude that endothelial cells have near-field antithrombotic properties that are enhanced by dipyridamole. Possible explanations for the near-field enhancement effect of dipyridamole are discussed in light of the published literature.