Defective cerebrovascular development in mice lacking TFPI is restored by activated protein C

The authors investigate whether excess activated protein C (aPC) can rescue cerebrovascular defects in mice lacking Tissue Factor Pathway Inhibitor (Tfpi-/-), which typically leads to embryonic lethality due to thrombin overproduction. They find that while aPC reduces glomeruloid body numbers and improves survival, it does not fully correct all cerebrovascular issues, indicating that TFPI plays a critical and non-redundant role in embryonic angiogenesis and thrombin regulation. The study highlights the complex interplay between coagulation factors and vascular development during embryogenesis.