What roles might PARs play in normal physiology and disease?
Because the connection between a specific PAR and a specific protease is best established for thrombin, this question is first considered in the context of PARs as detectors of coagulation proteases. Before launching into this conceit, it is important to state that the question of which proteases activate PARs in vivo has not been fully answered, and there will undoubtedly be more to the story. Thrombin is the main effector protease of the coagulation cascade, a series of zymogen conversions that are triggered when coagulation factors in plasma contact tissue factor expressed in the extravascular compartment or recruited to a site of injury. PARs are expressed by a variety of cell types in and around blood vessels (2), perhaps poised to detect activation of coagulation. PAR signaling largely accounts for the activation of platelets by thrombin, and such signaling plays a key role in hemostasis and thrombosis (2, 5, 6). Thus a role for PARs in mediating cellular responses to injury at t
