Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 546

Table 9.26. Antithrombogenic substances and clotting agents secreted by normal and damaged
endothelium, respectively. Blood circulation is preserved by a balance between hemorrhage and
thrombosis (HODE: hydroxyoctadecadienoic acid).

Antithrombotic agents Clotting factors

Protein-C Tissue factor

Protein-S von Willebrand factor

Thrombomodulin Multimerin

Heparan sulfate Platelet-activating factor

Antithrombin (AT or AT3) Adhesion molecules

Tissue plasminogen activator (tPA) Fibronectin

Urokinase (uPA) Collagen

Nitric oxide Endothelin

13HODE Clotting factors V and VIII

Prostacyclin (PGi2) Factors IX- and -X receptors

Prostaglandin-E2 Plasminogen activator inhibitor-1 and -2

Tissue factor pathway inhibitor

secondary hemostasis, i.e., a cascade of reactions that involves the set of coagulation
factors down to fibrin production to generate a clot after several minutes; (4) repair,
as the clot attracts and stimulates the growth of fibroblasts and smooth myocytes;
and (5) fibrinolysis leading to the clot dissolution.
Hemostasis relies on 4 interacting components to staunch blood, repair blood
vessel wall, and maintain adequate flow to downstream tissues: (1) vessel wall,
especially endothelium; (2) flowing platelets; (3) plasma coagulation factors and
their inhibitors; (4) fibrinolytic proteins; as well as (5) repair materials.
In normal vessels, endothelium prevents clotting (Table 9.26 ). Endothelial cells
have anticoagulant properties because they: (1) form a barrier between blood with its
platelets and clotting factors and vessel wall as well as (2) have thromboregulation
and anticoagulation function, i.e., inactivate thrombin and promote fibrinolysis in
normal conditions.
Endothelial plasmalemmal substances include thrombomodulin (TM),
protein-C (PC), tissue factor pathway inhibitor (TFPI), plasminogen activator
inhibitor-1 (PAI1 or serpin-E1; Table 9.27 ), and heparan sulfate proteoglycans.
On the surface of the endothelium, thrombomodulin is an integral membrane
cofactor in the thrombin-induced activation of protein-C in the anticoagulant
pathway. In fact, it interacts with multiple proteins to inhibit blood clotting
andinflammation[ 1001 ]. This proteoglycan, once bound to thrombin, promotes
thrombin-mediated activation of protein-C, which has anticoagulant, anti-apoptotic,
and anti-inflammatory activities. With cofactor protein-S synthesized by endothelial
cells, thrombomodulin activates protein-C that inhibits factors V and VIII as well as
protein-C and -S.