Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis.

For many years, the attention on tissue factor (TF) in human pathophysiology has been limited to its role as initiator of extrinsic coagulation pathway. Moreover, it was described as a glycoprotein located in several tissue including vascular wall and atherosclerotic plaque. However, in the last two decades, the discovery that TF circulates in the blood as cell-associated protein, microparticles (MPs) bound and as soluble form, is changing this old vessel-wall TF dogma. Moreover, it has been reported that TF is expressed by different cell types, even T lymphocytes and platelets, and different pathological conditions, such as acute and chronic inflammatory status, and cancer, may enhance its expression and activity. Thus, recent advances in the biology of TF have clearly indicated that beyond its known effects on blood coagulation, it is a "true surface receptor" involved in many intracellular signaling, cell-survival, gene and protein expression, proliferation, angiogenesis and tumor metastasis. Finally, therapeutic modulation of TF expression and/or activity has been tested with controversial results. This report, starting from the old point of view about TF as initiator of extrinsic coagulation pathway, briefly illustrates the more recent concepts about TF and thrombosis and finally gives an overview about its role beyond thrombosis and haemostasis focusing on the different intracellular mechanisms triggered by its activation and potentially involved in atherosclerosis.