INTRODUCTION

Platelets play an important role in the maintenance of hemostasis, in coagulation, and in the pathophysiology of thrombotic disease. They normally circulate in an unactivated state but respond quickly to injuries of blood vessel walls, alterations in blood flow, and biochemical stimuli. In response to endothelial injury, platelets accumulate at the site of injury, recruit other platelets, promote clotting, and form a hemostatic thrombus to prevent hemorrhage. Thromboregulatory systems of the vascular endothelium prevent or reverse inappropriate platelet accumulation, activation of coagulation factors, and formation of fibrin; they are the key to maintaining blood fluidity and the antithrombotic state. These inhibitory mechanisms modulate platelet function and act in a synergistic manner to prevent pathologic thrombus formation.

This chapter discusses platelet–endothelium interactions under normal physiologic conditions and in the setting of endothelial dysfunction. In addition, the principal inhibitors of platelet function and the central role of the normal endothelium in these inhibitory processes are summarized. The main endothelium-derived platelet inhibitors covered in this review include nitric oxide (NO), prostaglandins (PGs), and ectonucleotidases.

Vascular endothelium

The vascular endothelium is a highly active monolayer of cells that is crucial to the regulation of vascular function and structure. It is critically important in the local regulation of coagulation and fibrinolysis as well as in platelet activity.