PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) CONTENT IN PLATELETS FROM HEALTHY-INDIVIDUALS GENOTYPED FOR THE 4G 5G POLYMORPHISM IN THE PAI-1 GENE/

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 beta-thromboglobulin conte nts in platelets from the same individuals. A highly significant corre lation between PAI-1 activity and PAI-antigen was obtained, both in th e 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 plate let lysates (range 159 000-1190 000 U/mg). The calculated specific act ivity of PAI-1 in platelets seems to be higher than what could be expe cted 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 w ho were homozygous for the 4G allele seemed to have higher levels of P AI-1 activity and antigen in the platelet lysates, when compared to th e other genotypes. In platelet lysates, but not in plasma, a strong co rrelation was observed between the concentrations of PAI-1 and beta-th romboglobulin (r(2)=0.70, p<0.001). Vitronectin could be detected in t he platelet lysates in low concentrations (497+/-334 mu g/l). However, using a newly developed ELISA method for PAI-l-vitronectin complex we failed to demonstrate such a complex in the platelet lysates. Therefo re, the mechanism involved in stabilization of PAI-1 activity in the p latelets is at present not understood.