Tissue plasminogen activator (tPA) antigen in plasma: correlation with different tPA/inhibitor complexes

In many studies, tPA antigen has been a strong predictor of myocardial infarction. However, only a few percent of the total tPA antigen present in plasma samples taken at rest constitutes active tPA. The rest is enzymatically inactive and consists of a heterogeneous mixture of tPA in complex with inhibitors such as PAI-I, antiplasmin and C1 inhibitor. In the present study we developed specific two-site ELISA methods for determining the individual protease/inhibitor complexes constituting tPA antigen. We subsequently measured the concentrations of the different complexes in plasma samples taken from 30 healthy individuals. The results show that the concentration of the complex between tPA and PAT-1 in plasma correlated strongly with that of tPA antigen in plasma, as measured with a commercially available kit. Also the correlation between tPA/PAI-1 complex levels in plasma and the PAI-1 activity concentration was significant. However, no significant correlations were found between tPA antigen concentration and tPA/C1 inhibitor or tPA/antiplasmin concentrations in plasma.