title: A role for thrombin receptor signaling in endothelial cells during embryonic development.
abstract: 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.
authors.affiliation: Cardiovascular Research Institute, University of California at San Francisco (UCSF), San Francisco, California 94143.
authors.forename: C T
authors.initials: CT
authors.lastname: Griffin
authors.forename: Y
authors.initials: Y
authors.lastname: Srinivasan
authors.forename: Y W
authors.initials: YW
authors.lastname: Zheng
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: S R
authors.initials: SR
authors.lastname: Coughlin
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000502:physiology; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D004699:Endocardium / Q000196:embryology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005165:Factor V / Q000235:genetics / Q000502:physiology; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006470:Hemorrhage / Q000196:embryology; D006487:Hemostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011516:Prothrombin / Q000235:genetics / Q000502:physiology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013917:Thrombin / Q000502:physiology; D013925:Thromboplastin / Q000235:genetics / Q000502:physiology
chemical_list: D001779:Blood Coagulation Factors; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D005165:Factor V; D011516:Prothrombin; D005340:Fibrinogen; D013925:Thromboplastin; D013917:Thrombin; D002118:Calcium