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Science 293 (5535): 1666-1670

Copyright © 2001 by the American Association for the Advancement of Science

A Role for Thrombin Receptor Signaling in Endothelial Cells During Embryonic Development

Courtney T. Griffin,* Yoga Srinivasan,* Yao-Wu Zheng, Wei Huang, Shaun R. Coughlindagger

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.

Cardiovascular Research Institute, University of California at San Francisco (UCSF), San Francisco, California 94143
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: coughlin{at}cvrimail.ucsf.edu



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