Science · 2001 · 264 citations · 20 references
MedicineDevelopmental BiologyMolecular BiologyCell SignalingHemostasisSignal TransductionCoagulation CascadeCoagulation PhysiologyEndothelial ActivationFibrin FormationPlatelet ActivationThrombosisCoagulation Protease ActivationEndothelial Contribution To ThrombosisEndothelial Function ModulationEndothelial Regulation Of CoagulationEndothelium-dependent Coagulation RegulationPlatelet-endothelial InteractionsThrombin-mediated Platelet ActivationTissue Injury Response
The coagulation protease thrombin triggers fibrin formation, platelet activation, and other cellular responses at sites of tissue injury. We report a role for PAR1, a protease-activated G protein-coupled receptor for thrombin, in embryonic development. Approximately half of Par1-/- mouse embryos died at midgestation with bleeding from multiple sites. PAR1 is expressed in endothelial cells, and a PAR1 transgene driven by an endothelial-specific promoter prevented death of Par1-/- embryos. Our results suggest that the coagulation cascade and PAR1 modulate endothelial cell function in developing blood vessels and that thrombin's actions on endothelial cells-rather than on platelets, mesenchymal cells, or fibrinogen-contribute to vascular development and hemostasis in the mouse embryo.
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Ramesh A. Shivdasani, Margery Rosenblatt, Dorothea Zucker‐Franklin et al. · Cell · 1995 · 700 citations · Full text
Role of tissue factor in embryonic blood vessel development
Peter Carmeliet, Nigel Mackman, Lieve Moons et al. · Nature · 1996 · 677 citations
Defective platelet activation in Gαq-deficient mice
Stefan Offermanns, Christopher F. Toombs, Yi-Hui Hu et al. · Nature · 1997 · 562 citations
Medicine, Genetics, Hematology +12
Role of the thrombin receptor in development and evidence for a second receptor
Andrew J. Connolly, Hiroaki Ishihara, Mark L. Kahn et al. · Nature · 1996 · 509 citations