Factor VIIa Interaction With Tissue Factor and Endothelial Cell Protein C Receptor on Cell Surfaces

Abstract

Factor VIIa (FVIIa) is the enzyme that triggers activation of the clotting cascade that eventually leads to fibrin deposition and platelet activation. Association of FVIIa with its cellular receptor, tissue factor (TF), which greatly increases FVIIa enzymatic activity, is essential for the effective initiation of the coagulation pathway. FVIIa also complexes with endothelial cell protein C receptor (EPCR), but this association does not increase the enzymatic activity of FVIIa. This article reviews current knowledge of FVIIa interaction with TF and EPCR on cell surfaces with a specific focus on how these interactions may contribute to FVIIa and TF clearance, thereby regulating TF-FVIIa activity.

Multiple receptor-mediated functions of activated protein C

“…In addition, EPCR functions as a receptor for coagulation factors VIIa (68,(71)(72)(73) and Xa (74). EPCR-FVIIa interactions may sequester FVIIa from procoagulant phosphatidylserine-rich membrane domains, thereby exerting a FVIIa-dependent anticoagulant activity (73,75), and modulate the bioavailability of therapeutically administered recombinant FVIIa (76).…”

CD248 enhances tissue factor procoagulant function, promoting arterial and venous thrombosis in mouse models

“…These include, for example, endothelial protein C receptor (EPCR), β1-integrin, protease activated receptors (PARs), and the insulin-like growth factor 1 receptor (IGF-1R). [9][10][11][12] Not surprisingly, excess expression of TF has been implicated in the pathogenesis of several disorders, including arterial and venous thrombosis, cardiovascular disease, atherosclerosis, obesity, cancer, and coagulopathies associated with sepsis and pregnancy. [13][14][15][16] Defining the mechanisms by which TF is regulated is therefore of major interest, as this may yield therapeutic insights.…”

“…Beyond coagulation, TF also has functions in inflammation, cell proliferation and differentiation, apoptosis, cell motility, and angiogenesis, mediated via direct and indirect interplay with other cellular components. These include, for example, endothelial protein C receptor (EPCR), β1‐integrin, protease activated receptors (PARs), and the insulin‐like growth factor 1 receptor (IGF‐1R) 9‐12 . Not surprisingly, excess expression of TF has been implicated in the pathogenesis of several disorders, including arterial and venous thrombosis, cardiovascular disease, atherosclerosis, obesity, cancer, and coagulopathies associated with sepsis and pregnancy 13‐16 .…”