Platelet PAR1 receptor density--correlation to platelet activation response and changes in exposure after platelet activation

Thromb Res. 2008;121(5):681-8. doi: 10.1016/j.thromres.2007.06.010. Epub 2007 Aug 1.

Abstract

Introduction: A polymorphism (-14 A/T) affecting PAR1 expression on the platelet surface has recently been identified. A two-fold variation in receptor density, which correlated with the platelet response to PAR1-activating peptide (PAR1-AP), has been reported.

Materials and methods: We used flow cytometry to measure the correlation between the number of PAR1 receptors and platelet activation. We also measured the changes in receptor exposure after platelet activation with PAR1-AP, ADP, PAR4-AP or a collagen-related peptide (CRP).

Results: In our study, the PAR1 receptor number varied almost four-fold, from 547 to 2063 copies/platelet (mean+/-S.D. 1276+/-320, n=70). The number of PAR1 receptors on resting platelets correlated to platelet fibrinogen binding and P-selectin expression following platelet activation with PAR1-AP (r(2)=0.30, p<0.01 and r(2)=0.15, p<0.05, respectively, n=36). The correlation was not improved by exclusion of the ADP-component from the PAR1-AP-induced response. We found a trend, but no statistically significant differences in PAR1 receptor number and platelet reactivity between A/A individuals and T/A or T/T individuals. Ex vivo activation with PAR1-AP decreased PAR1 surface exposure to 71+/-19% of the exposure on resting platelets (mean+/-S.D., p<0.01, n=19), while activation by ADP, PAR4-AP or CRP significantly increased the exposure, to 151+/-27%, 120+/-21% and 138+/-25%, respectively (n=11, 11 and 10).

Conclusions: This study shows a large variation in PAR1 receptor number in healthy individuals, a variation correlated to the platelet activation response. We found a significant reduction in PAR1 surface exposure after adding PAR1-AP, while activation with ADP, PAR4-AP or CRP increased the exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Platelets / chemistry*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation*
  • Platelet Aggregation
  • Receptor, PAR-1 / blood*

Substances

  • Receptor, PAR-1