Plasminogen activator inhibitor-1 (PAI-1) content in platelets from healthy individuals genotyped for the 4G/5G polymorphism in the PAI-1 gene

Abstract

We have studied PAI-1 activity and antigen content in platelets and in plasma from 37 healthy individuals who were also genotyped for the 4G/5G polymorphism in the PAI-1 promoter region. The PAI-1 data obtained were compared with the vitronectin and the β-thromboglobulin contents in platelets from the same individuals. A highly significant correlation between PAI-1 activity and PAI-antigen was obtained, both in the plasma samples (p<0.0001) and in the platelet lysates (p<0.001). The specific activity of PAI-1 was higher in plasma than in the platelet lysates, but interindividual variation was more pronounced among platelet lysates (range 159000-1190000 U/mg). The calculated specific activity of PAI-1 in platelets seems to be higher than what could be expected from theoretical considerations regarding half-life of platelets in the circulation and conversion of functional PAI-1 to latent PAI-1. On analysis of the influence of the 4G/5G polymorphism, individuals who were homozygous for the 4G allele seemed to have higher levels of PAI-1 activity and antigen in the platelet lysates, when compared to the other genotypes. In platelet lysates, but not in plasma, a strong correlation was observed between the concentrations of PAI-1 and β-thromboglobulin (r²=0.70, p<0.001). Vitronectin could be detected in the platelet lysates in low concentrations (497±334 μg/1). However, using a newly developed ELISA method for PAI-1—vitronectin complex we failed to demonstrate such a complex in the platelet lysates. Therefore, the mechanism involved in stabilization of PAI-1 activity in the platelets is at present not understood.

Key Words:

• platelets
• PAI-1
• PAI-1 polymorphism
• β-thromboglobulin
• vitronectin