Editorial Commentary: Tissue factor expression by the endothelium: Coagulation or inflammation?

In this issue of Trends in Cardiovascular Medicine, Witkowski et al. review studies proposing that tissue factor (TF) links coagulation and inflammation. Importantly, TF is a cofactor for the coagulation protease factor VIIa(FVIIa) and therefore it is theTF:FVIIa complex that initiates the coagulation cascade. Interestingly, it has structural homology to members of the class 2 cytokine receptor family. The primary role of the TF:FVIIa complex is to maintain hemostasis. Indeed, a complete deficiency of either TF or FVII is not compatible with life. Activation of the coagulation cascade by the TF:FVIIa complex generates a number of serine proteases that can activate cells and enhance inflammation by cleavage of protease activated receptors (PARs). For instance, FXa activates PAR2 and thrombin activates PAR1. Therefore, the TF:FVIIa complex has a secondary role as an enhancer of inflammation