PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways.
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.
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, Berkshire RG6 6UB, UK. c.i.jones@reading.ac.uk
Chris I
CI
Jones
Stephen F
SF
Garner
Leonardo A
LA
Moraes
William J
WJ
Kaiser
Angela
A
Rankin
Willem H
WH
Ouwehand
Alison H
AH
Goodall
Jonathan M
JM
Gibbins
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D002352:Carrier Proteins; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; C435908:collagen-related peptide; C098341:platelet membrane glycoprotein VI; D000244:Adenosine Diphosphate; D013917:Thrombin; D002118:Calcium