Tissue Factor Expression by the Endothelium

Tissue factor (TF) is the primary cellular initiator of blood coagulation (1). It is constitutively expressed around blood vessels and plays an essential role in hemostasis. Under normal conditions, the surface of the endothelium is antithrombotic due to the binding of the anticoagulant protein tissue factor pathway inhibitor (TFPI) and the absence of TF. In addition, “resting” endothelium expresses the receptors thrombomodulin and endothelial protein C receptor, which permits the generation of the anticoagulant protein, activated protein C. However, under pathological conditions, the surface of the endothelium becomes prothrombotic due to the induction of TF and the downregulation of anticoagulants. Numerous studies have documented the induction of TF in cultured vascular endothelial cells (ECs) in response to a variety of agonists. Other studies have described TF expression on the endothelium in vivo, although some controversy exists about whether or not ECs express TF in vivo. This chapter reviews our current understanding of the intracellular regulatory pathways that control TF gene expression in cultured ECs. We also evaluate the data on TF expression by ECs in vivo. TISSUE FACTOR EXPRESSION BY ENDOTHELIAL CELLS IN VITRO Induction of Tissue Factor Expression in Cultured Endothelial Cells The majority of the studies on TF expression in cultured ECs have been performed using human umbilical vein ECs (HUVECs). Quiescent cultured ECs express very lowor undetectable levels of TF. The first description of TF expression by ECs was in 1977, by a group that showed a transient induction of TF activity in ECs after subculture (2). Since this time, a variety of agents have been shown to induce TF expression in ECs (Table 104–1).