Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-α₂-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008. Under basal conditions plasma PAI activities and plasma concentrations of PAI-1 antigen were both significantly negatively correlated with plasma concentrations of PAP-complex (r(s) = -0.32; P < 0.02 and r(s) = -0.42; P < 0.002, respectively). After stimulation of the fibrinolytic system by infusion of DDAVP, plasma PAI activities and plasma concentrations of PAI-1 antigen were also significantly negatively correlated with plasma concentrations of PAP-complex (r(s) = -0.41; P < 0.002 and r(s) = -0.33; P < 0.009, respectively). Our results indicate that PAI-1 regulates formation of plasmin in patients with ischaemic heart disease. These observations support that PAI-1 may play a critical role in the evolution of thrombosis.