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


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.
Department of Biomedicine and Surgery, Division of Clinical Chemistry, University Hospital, SE-581 85 Linköping, Sweden. sofra@ibk.liu.se
Sofia
S
Ramström
Karin Vretenbrant
KV
Oberg
Finn
F
Akerström
Camilla
C
Enström
Tomas L
TL
Lindahl
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010974:Platelet Aggregation; D044463:Receptor, PAR-1 / Q000097:blood*
D044463:Receptor, PAR-1