Role of tissue factor in haemostasis, thrombosis, angiogenesis and inflammation: lessons from low tissue factor mice.

Tissue factor (TF) contributes to a variety of biological processes by generating coagulation proteases and by the activation of protease activated receptors (PARs). Studies, using low TF mice, have provided us with novel insights into the role of TF in tissue-specific haemostasis. Low TF mice exhibit defects in the uterus, placenta, heart and lung, which are all tissues that normally express high levels of TF. We propose that these observed defects are primarily due to a reduction in the level of TF to below a critical threshold that is required to maintain adequate haemostasis. Nevertheless, a reduction in TF:FVIIa-dependent signaling may also reduce cell survival and/or compromise the integrity of the vasculature in these organs. Low TF mice are also a useful tool to study the role of TF and the coagulation cascade in other processes, such as thrombosis, inflammation and angiogenesis.