The control of hemostasis. Role of endothelium in the regulation of inhibitory and catabolic pathways.

The role of the microvascular endothelium in the integration of inhibitory and catabolic pathways of hemostasis is discussed in light of recent findings of direct biochemical links between endothelium and regulatory plasma proteins. These findings include the following: (1) On the vascular endothelium, a cofactor for antithrombin III (with an activity comparable to stationary phase heparin) catalyzes thrombin inhibition in vivo. (2) A second cofactor on endothelium binds thrombin in a manner that enhances by several orders of magnitude the ability of thrombin to activate protein C. (3) Activated protein C has both anticoagulant and catabolic activities; anticoagulant activity results from the susceptibility of factors Va and VIIIa to inactivation by activated protein C, whereas catabolic activity arises from the stimulation by activated protein C of the release from endothelium of fibrin-dependent plasminogen activator. (4) Because it requires fibrin as a cofactor, the plasminogen activator lyses clots without provoking fibrinogenolysis. Location of these activities on endothelium separates coagulation in time and space from catabolic pathways, and provides for their expression after the initiation of hemostasis.