This study deals with the effect of fibrin on the transformation of Glu-plasminogen to Glu-plasmin during fibrinolysis. It focuses particularly on changes in fibrin effector function caused by plasmin-catalysed fibrin degradation. Conversion of 1251-labelled Glu-plasminogen to Glu-plasmin was catalysed by urokinase or tissue plasminogen activator, in the presence of different preparations of progressively degraded fibrin. Plasmin catalysis of Glu-plasminogen and the fibrin (derivative) effector was inhibited by aprotinin.The presence of intact fibrin enhanced the rate of Glu-plasmin formation catalysed by tissue plasminogen activator, but not by urokinase. The presence of initially plasmin-cleaved fibrin, however, increased the rates of Gluplasmin formation with both activators, as compared to those found with intact fibrin. The rate enhancements induced by initial plasmin degradation of the fibrin effector were associated with an increase in its affinity to both Glu-plasminogen and tissue plasminogen activator, suggesting causal relationships. The weak binding of urokinase was unaffected by fibrin degradation, indicating that effector function was solely exerted on the Glu-plasminogen moiety of urokinase-activated systems. Further degradation of fibrin decreased the stimulating effect on Glu-plasmin formation. This decrease occurred at an earlier stage of degradation with tissue plasminogen activator than with urokinase, indicating that greater integrity of the fibrin effector is necessary for its optimal interaction with the tissue plasminogen activator than with Glu-plasminogen.Concentrations of tranexamic acid that saturate low-affinity lysine-binding sites nearly completely dissociated the binding of Glu-plasminogen to degraded fibrin, but not to intact fibrin. In analogy with the binding of lysine analogues to these sites, the conformation of Glu-plasminogen may be altered by binding to degraded fibrin, thus giving rise to the increased activation rate.The resolution of fibrin in mammals may be caused either by the enzyme plasmin or by leucocytic enzymes [I, 21. Recent evidence indicates that plasmin may play an important role in early intravenous fibrin degradation [3]. Plasmin is formed from its proenzyme plasminogen by a plasminogen-activatorcatalysed reaction. There are two immunologically distinct types of plasminogen activator [4, 51. One is tissue-type plasminogen activator, t-PA (in this work represented by melanoma cell plasminogen activator) and the other, urokinase. Their complete amino acid sequences have recently been determined [6, 71.Activation of plasminogen proceeds along two alternative pathways [8, 91. One is an activator-catalysed conversion of Glu-plasminogen to Glu-plasmin followed by an autocatalytic conversion of Glu-plasmin to Lys-plasmin. The other is plasmin-catalysed conversion of Glu-plasminogen to Lys-plasminogen followed by activator-catalysed conversion of Lysplasminogen to Lys-plasmin. The conversion of Glu-plasminogen to Glu-plasmin can be regarded as an initial obligatory...
In a previous study we have shown that plasminogen activator inhibitor (PAI) decreased in normal healthy volunteers during the day from 6.3±3.1 IU/ml (X±ISD) at 7.15 a.m. to 2.8±2.3 IU/ml at 3 p.m.The aim of the present study was to investigate the effect of major elective abdominal surgery on PAI. Eight patients received 2,500 Xal units of low molecular weight heparin (LogiparinTM) (Gr.l) and 7 patients received 3,500 Xal units of Logiparin (Gr.2). The PAI activity was measured amidolytically according to Chmielewska et al 1983.The plasma level of PAI (IU/ml) was (X±1SD):We found that PAI did not decrease during the day of surgery but the PAI level was significantly higher on the morning after surgery than the previous morning (p ‹ 0.05). The 5th postoperative day the PAI level had returned to pre-operative values in the morning, but did not decrease during the day as seen in normal volunteers. The PAI levels were not influenced by the different doses of heparin.Thus PAI was found to increase postoperatively and the normal decrease in PAI during the day seems to be abolished for at least five days after surgery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.