Vascular protease receptors: integrating haemostasis and endothelial cell functions

The endothelium plays a crucial dynamic role as a protective interface between blood and the underlying tissues during the haemostatic process, which maintains blood flow in the circulation and prevents life-threatening blood loss. Following vessel wall injury with initial platelet adhesion and aggregation to exposed subendothelial extracellular matrix, the initiation, amplification, and control of haemostasis depend on structurally unrelated membrane-associated receptors for blood coagulation proteases including tissue factor, G-protein-coupled protease-activatable receptors, thrombomodulin, and protein C receptor, respectively. In addition to their regulatory role in haemostasis, the respective (pro-)enzyme ligands such as Factors VIIa and Xa, thrombin or protein C mediate specific signalling pathways in vascular cells related to migration, proliferation or adhesion. The functional importance of these receptors beyond haemostasis has been manifested by various lethal and pathological phenotypes in knock-out mice. These protease receptors thereby provide important molecular links in the vascular system and serve to integrate haemostasis with endothelial cell functions which are relevant for the (patho-)physiological responses to injury or inflammatory challenges.