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Tissue factor pathway inhibitor is required for cerebrovascular development in mice
Susan A Maroney1, Randal J Westrick2,3,4, Audrey C Cleuren4,5,6,7
1Versiti Blood Research Institute, Milwaukee, WI.
Blood
|August 1, 2020
Summary
Tissue factor pathway inhibitor (TFPI) is crucial for central nervous system (CNS) vascular development. Its absence causes brain pathology, which is reversed by removing factor V (FV), highlighting TFPI
Area of Science:
- Coagulation cascade regulation
- Embryonic vascular development
- Central nervous system (CNS) development
Background:
- Tissue factor pathway inhibitor (TFPI) regulates blood coagulation proteases, including thrombin generation.
- TFPI and factor V (FV) are essential for embryogenesis, but their roles in vascular development are not fully understood.
Purpose of the Study:
- To investigate the interplay between TFPI and FV in regulating hemostasis and vascular development during embryogenesis.
- To elucidate the specific role of TFPI in CNS vascular development.
Main Methods:
- Histological analysis of Tfpi-/- and Tfpi-/-F5-/- mouse embryos.
- Comparative analysis of tissue and CNS development in genetically modified mouse models.
Main Results:
- Tfpi-/- embryos exhibited normal development except for the CNS, which showed stunted brain growth, meningeal defects, and severe vascular pathology (glomeruloid bodies, fibrin, hemorrhage).
- Removal of FV in Tfpi-/-F5-/- embryos completely resolved the observed brain pathology.
- These findings suggest TFPI modulates FV-dependent procoagulant activity impacting cerebrovascular development.
Conclusions:
- TFPI plays a previously unrecognized role in CNS vascular development.
- TFPI activity likely mitigates excessive thrombin signaling that affects cerebral vascular development, particularly by dampening FV-dependent procoagulant activity.
