A pathway of coagulation on bovine capillary endothelial cells

In this report cultured bovine capillary endothelial cells are demonstrated to specifically bind factors IX and X and also their activated forms. Bound factor IXa and cell-associated factor VIII can activate factor X. The product of this reaction, factor Xa, can then interact with a factor V-like molecule expressed by capillary endothelial cells promoting thrombin formation. The thrombin formed can cleave fibrinogen leading to release of fibrinopeptide A and clot formation. Endotoxin-treatment of capillary endothelial cells leads to induction of tissue factor activity which, in the presence of factor VIIa, promotes activation of factors IX and X. The amount of factor Xa formed endotoxin-treated endothelial cells incubated with factors VIIa, IX, VIII and X, is 8 times greater than cells incubated with factors VIIa and X alone. This indicates that on the perturbed endothelial cell surface factors VIII and IX do play an important role in factor X activation by the tissue factor pathway. The perturbed capillary endothelial cell can thus provide a model of the thrombotic state promoting initiation and propagation of a procoagulant pathway leading to thrombin formation. This pathway of coagulation is endothelial cell-dependent, since it requires expression of tissue factor and factor V by capillary endothelial cells, as well as interaction of coagulation factors with the surface of capillary endothelial cells.