PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways

Jones, Chris I.; Garner, Stephen F.; Moraes, Leonardo A.; Kaiser, William J.; Rankin, Angela; Bloodomics Consortium,; Ouwehand, Willem H.; Goodall, Alison H.; Gibbins, Jonathan M.

doi:10.1016/j.febslet.2009.10.037

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Volume 583, Issue 22 , Pages 3618-3624, 19 November 2009

PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways

Edited by Beat Imhof

Chris I. Jones
- Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading, Berkshire, RG6 6UB, UK
- Corresponding author.
Stephen F. Garner
- Department of Haematology, University of Cambridge and NHS Blood and Transplant, Cambridge, UK
Leonardo A. Moraes
- Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading, Berkshire, RG6 6UB, UK
William J. Kaiser
- Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading, Berkshire, RG6 6UB, UK
Angela Rankin
- Department of Haematology, University of Cambridge and NHS Blood and Transplant, Cambridge, UK
Bloodomics Consortium
Willem H. Ouwehand
- Department of Haematology, University of Cambridge and NHS Blood and Transplant, Cambridge, UK
- Human Genetics Department, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Alison H. Goodall
- Cardiovascular Sciences, University of Leicester, UK
Jonathan M. Gibbins
- Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Building, Whiteknights, Reading, Berkshire, RG6 6UB, UK

Received 11 June 2009; received in revised form 7 October 2009; accepted 8 October 2009. published online 20 October 2009.

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits platelet response to collagen and may also inhibit two other major platelet agonists ADP and thrombin although this has been less well explored. We hypothesized that the combined effect of inhibiting these three platelet activating pathways may act to significantly inhibit thrombus formation. We demonstrate a negative relationship between PECAM-1 surface expression and platelet response to cross-linked collagen related peptide (CRP-XL) and ADP, and an inhibitory effect of PECAM-1 clustering on platelet response to CRP-XL, ADP and thrombin. This combined inhibition of multiple signaling pathways results in a marked reduction in thrombus formation.

Keywords: Platelets, PECAM-1, Collagen, ADP, Thrombin, Thrombus