The cleaved peptide of PAR1 is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin

J Vasc Surg. 2003 Feb;37(2):440-5. doi: 10.1067/mva.2003.129.


Purpose: Platelet-endothelial cell adhesion is an important pathologic response to vessel injury or inflammation. On binding to its endothelial or platelet G protein-linked seven-transmembrane domain receptor, protease-activated receptor-1 (PAR1), thrombin releases a 41-amino acid peptide (TR(1-41)). We examined the effect of TR(1-41) on platelet activation and on platelet-endothelial cell adhesion.

Methods: A monolayer of confluent human saphenous vein endothelial cells was incubated with washed human platelets. Platelets were stimulated with either TR(1-41), TR(21-41), scrambled TR(1-41), adenosine diphosphate (ADP)-epinephrine (EPI), thrombin, or thrombin receptor activating peptide (TRAP). Platelet activation was identified with flow cytometry. The magnitude of platelet-endothelial cell adhesion was determined with a laser scanning cytometer that scanned the monolayer of endothelial cells and identified fluorescently bound platelets.

Results: Maximal thrombin stimulation (0.1 U/mL) induced a threefold increase in platelets bound to endothelial cells compared with buffer alone. Stimulation with TR(1-41) (20 mmol/L) tripled the number of platelets bound to endothelial cells compared with thrombin. Scrambled sequence of TR(1-41) (20 mmol/L) and TR(21-41) (20 mmol/L), neither of which induces platelet activation, had minimal effect on platelet adhesion. Both TRAP (20 mmol/L) and ADP-EPI (20 mmol/L) induced less platelet-endothelial cell adhesion than did thrombin. TR(1-41)-induced platelet-endothelial cell adhesion was partially blocked by glycoprotein (GP)IIb-IIIa-specific monoclonal antibody, 10E5 (10 mg/mL).

Conclusions: TR(1-41), the cleaved peptide of PAR1, is a more potent stimulant of platelet-endothelial cell adhesion than is thrombin, TRAP, or ADP-EPI, and this adhesion is at least in part mediated by the platelet GPIIb-IIIa receptor.

MeSH terms

  • Cell Adhesion / drug effects*
  • Cell Adhesion / physiology
  • Cell Division / drug effects*
  • Cell Division / physiology
  • Endothelium / drug effects*
  • Endothelium / physiopathology
  • Hemostatics / pharmacology*
  • Humans
  • In Vitro Techniques
  • Peptide Fragments / pharmacology*
  • Platelet Adhesiveness / drug effects*
  • Platelet Adhesiveness / physiology
  • Receptor, PAR-1
  • Receptors, Thrombin / drug effects*
  • Receptors, Thrombin / physiology
  • Saphenous Vein / drug effects
  • Saphenous Vein / physiopathology
  • Thrombin / pharmacology*
  • Venous Thrombosis / physiopathology*


  • Hemostatics
  • Peptide Fragments
  • Receptor, PAR-1
  • Receptors, Thrombin
  • thrombin receptor peptide (1-41)
  • Thrombin