Some things I thought I knew about tissue factor that turn out to be wrong.

Tissue factor (TF) plays an critical role in hemostasis and some types of thrombosis. However, it also has roles beyond its coagulant function. TF is a member of the cytokine receptor superfamily. Its expression is upregulated by inflammatory cytokines and thus links injury and inflammation with thrombosis. TF levels have been linked with expression of a malignant phenotype and with angiogenesis. While the mechanisms of these activities are not thoroughly understood, some are related to generation of activated coagulation factors. Others appear to result from signaling events mediated directly by TF or indirectly by interaction with other receptors. Under normal conditions, blood vessels are encircled by a coat of TF due to expression by pericytes and adventitial cells. Based on the literature, we expected that vascular and extravascular TF expression would be up-regulated near sites of injury and during wound healing and angiogenesis. Surprisingly, TF disappears from around blood vessels near a cutaneous punch biopsy wound within a day, only returning six to eight days later. Furthermore, the highly vascular granulation tissue that fills the healing wound also lacks TF. At no point could we detect endothelial TF expression in any of our skin specimens. Thus, endothelial or peri-vascular TF does not seem to play a role in normal wound angiogenesis. The observed down-regulation of TF expression may serve to prevent thrombosis of developing neovessels and contribute to the well-recognized tendency of granulation tissue to bleed readily and profusely.