Platelets, Vessel Wall, and the Coagulation System

Platelet-endothelium interactions play a critical role in the maintenance of vascular integrity and in the regulation of thrombotic and inflammatory events. Platelets support endothelial barrier function, thereby restricting the loss of macromolecules and blood cells from the circulation. Endothelial cells in turn maintain platelet reactivity low to prevent platelet adhesion and intravascular thrombus formation. Platelet control mechanisms involve nonadhesive properties of the endothelial cell membrane, inactivation of platelet stimuli by endothelial-bound proteins, and production of prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF), mediators that are well known to inhibit platelet reactivity. Importantly, the synthesis of PGI2 and EDRF in endothelial cells can be amplified by compounds produced and/or released upon platelet activation (thrombin, PGH2, adenine nucleotides, serotonin), representing a major feedback mechanism in thromboregulation and limiting excessive platelet aggregation. When the antithrombotic balance of the endothelium is disturbed, platelets may attach to endothelial cells through a mechanism involving adhesion receptors. Activated platelets also express interleukin-1 (IL-1) on their surface and release transforming growth factor-β (TGF-β), which cause endothelial cells to synthesize adhesion molecules, cytokines, and plasminogen activator inhibitor type 1 (PAI-1), all of which potentiate inflammatory and thrombotic events.