2006 Russell Ross Memorial Lectureship in Vascular Biology—Tissue Factor as a Mediator and Marker of Cardiovascular Disease: New Roles for an Old Molecule
Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation and plays a critical role in hemostasis and thrombosis. TF expression is linked to inflammatory and proliferative responses, in part through the generation of thrombin, an important mediator of growth and inflammation. Recent data have implicated TF as an important mediator of angiogenesis, intimal hyperplasia, ischemia-reperfusion injury, and cardiac fibrosis. Our data also suggest that TF may mediate the intimal and proliferative responses in a rat model of pulmonary arterial hypertension. It is likely that the effects of TF on these processes are particularly related to its role in mediating inflammation. Although TF was once thought to act exclusively as a cell-associated molecule, TF is present in several forms in the circulation. The predominant form is in microparticles (MPs) that presumably bud from the surface of many cell types, such as endothelium, macrophages, and smooth muscle cells, as a part of normal cellular homeostasis or are released during cell death or injury. TF-containing MPs have been found in association with naturally occurring and experimental thrombi. In addition to MPs, there is a naturally occurring, soluble form of human TF generated by alternative splicing. This splice variant has a novel C-terminus, lacks a transmembrane domain, and is present in blood. There are conflicting data as to the role of TF-containing MPs in mediating thrombosis. However, recent studies have found that blood TF is elevated in a variety of cardiovascular diseases, and blood TF levels may have predictive value for secondary events in patients with previous myocardial infarction and for venous thromboembolism.