Tissue factor pathway inhibitor is required for cerebrovascular development in mice.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
14 01 2021
14 01 2021
Historique:
received:
31
03
2020
accepted:
14
07
2020
pubmed:
1
8
2020
medline:
20
4
2021
entrez:
1
8
2020
Statut:
ppublish
Résumé
Tissue factor pathway inhibitor (TFPI) inhibits proteases in the blood coagulation cascade that lead to the production of thrombin, including prothrombinase (factor Xa [FXa]/FVa), the catalytic complex that directly generates thrombin. Thus, TFPI and FV are directly linked in regulating the procoagulant response. Studies using knockout mice indicate that TFPI and FV are necessary for embryogenesis, but their contributions to vascular development are unclear. We performed extensive histological analyses of Tfpi-/- and Tfpi-/-F5-/- mouse embryos to investigate the importance of the interplay between TFPI and FV in regulating hemostasis and vascular development during embryogenesis. We observed normal tissue development throughout Tfpi-/- embryos, except in the central nervous system (CNS). The CNS displayed stunted brain growth, delayed development of the meninges, and severe vascular pathology characterized by the formation of glomeruloid bodies surrounding areas of cellular death, fibrin deposition, and hemorrhage. Removing FV from Tfpi-/- embryos completely ameliorated their brain pathology, suggesting that TFPI dampens FV-dependent procoagulant activity in a manner that modulates cerebrovascular development. Thus, we have identified a previously unrecognized role for TFPI activity within the CNS. This TFPI activity likely diminishes an effect of excess thrombin activity on signaling pathways that control cerebral vascular development.
Identifiants
pubmed: 32735640
pii: S0006-4971(21)00041-0
doi: 10.1182/blood.2020006054
pmc: PMC7820871
doi:
Substances chimiques
Lipoproteins
0
lipoprotein-associated coagulation inhibitor
0
Factor V
9001-24-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
258-268Subventions
Organisme : NHLBI NIH HHS
ID : R35 HL135793
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130678
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117132
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007209
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135035
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI133561
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL068835
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133348
Pays : United States
Informations de copyright
© 2021 by The American Society of Hematology.
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