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 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 159,000-1,190,000 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 beta-thromboglobulin (r2 = 0.70, p < 0.001). Vitronectin could be detected in the platelet lysates in low concentrations (497 +/- 334 micrograms/l). 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.
Nordenhem
A
A
Department of Clinical Chemistry and Blood Coagulation, Karolinska Hospital, Stockholm, Sweden.
Wiman
B
B
D001792:Blood Platelets / Q000378:metabolism*; D002940:Circadian Rhythm; D005838:Genotype; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D011110:Polymorphism, Genetic; D012016:Reference Values; D019096:Vitronectin / Q000097:blood; D001620:beta-Thromboglobulin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin; D001620:beta-Thromboglobulin