SummaryTo determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTC A), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p <0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p <0.05 to p <0.0005).

No abstract

No abstract

No abstract

It could be shown previously by us and others that the PA activity of purified VPA is increased in the presence of fibrin, while the activity of UK remains unchanged. However, there had been some discussion on the mechanisms involved and the relative potency of the different PAs in man. In the present study kinetic analysis of plasminogen activation with different PAs was performed in the presence and absence of fibrin.Human UK (urine, Mr=56.000) , VPA (cadaver vessel eluates) , PK (HF-fragments activated) were purified to apparent homogeneity, and active sites were determined by 3H-DFP incorporation. Plasminogen activation was evaluated by incubation of different amounts of PAs with Glu-plasminogen at different substrate concentrations with and without fibrin (fibrinogen- Sepharose treated with thrombin) at 37°C for 3 to 120 minutes; the plasmin generated was measured by a synthetic para- nitroanilide substrate.Under these conditions VPA exhibited an apparent KM≃0.5 μM and a kcat≃0.15 s-1. In the presence of fibrin KM decreased significantely (<<0.01 μM) while kcat remained unchanged; untreated fibrinogen-Sepharose had no effect. UK, on the other hand, showed an apparent KM≃1 μM and a kcat≃0.5 s-1 which were both unaffected by fibrin. PK cleaved plasminogen with an apparent KM≃0.2 μM and a kcat≃0.004 s-1 regardless of the presence of fibrin. Preliminary data using intact HF together with kaolin and phospholipids revealed an apparent KM for plasminogen activation of that mixture of 3.5 μM and a kcat≃0.07 s-1 which were again unaffected by fibrin.From these data it can be concluded that in the absence of fibrin UK is a more effective PA than the others, while in the presence of fibrin VPA is by fare the most effective one. From kinetic analysis PK and HF should play only a minor role in plasminogen activation.