Publication Date:
2001-09-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffin, C T -- Srinivasan, Y -- Zheng, Y W -- Huang, W -- Coughlin, S R -- HL44907/HL/NHLBI NIH HHS/ -- HL65590/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 31;293(5535):1666-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Institute, University of California at San Francisco (UCSF), San Francisco, California 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11533492" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blood Coagulation
;
Blood Coagulation Factors/physiology
;
Blood Vessels/*embryology/metabolism
;
Calcium/metabolism
;
Crosses, Genetic
;
*Embryonic and Fetal Development
;
Endocardium/embryology/metabolism
;
Endothelium, Vascular/cytology/*embryology/metabolism
;
Factor V/genetics/physiology
;
Female
;
Fibrinogen/genetics/physiology
;
Fibroblasts/metabolism
;
Hemorrhage/embryology
;
Hemostasis
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred Strains
;
Mice, Transgenic
;
*Neovascularization, Physiologic
;
Phenotype
;
Prothrombin/genetics/physiology
;
Receptor, PAR-1
;
Receptors, Thrombin/deficiency/genetics/*physiology
;
*Signal Transduction
;
Thrombin/physiology
;
Thromboplastin/genetics/physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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