A role for thrombin receptor signaling in endothelial cells during embryonic development.
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.
Griffin
C T
CT
Cardiovascular Research Institute, University of California at San Francisco (UCSF), San Francisco, California 94143.
Srinivasan
Y
Y
Zheng
Y W
YW
Huang
W
W
Coughlin
S R
SR
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
D001779:Blood Coagulation Factors; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D005165:Factor V; D011516:Prothrombin; D005340:Fibrinogen; D013925:Thromboplastin; D013917:Thrombin; D002118:Calcium