Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential role of platelets in platelet rich plasma clot lysis induced by tissue plasminogen activator (t-PA) was investigated. At the various concentrations of both single chain t-PA (sct-PA) and two chain t-PA (tct-PA) (1.5nM, 3nM, and 6nM), we compared the t-PA mediated lysis time of platelet rich plasma clot (PRP-clot) with that of platelet poor plasma clot (PPP-clot). At the concentrations ranged from 1.5 to 6 nM of both types of t-PA, the clot lysis time of PRP-clot was longer than that of PPP-clot. This elongation was more significant in the tct-PA induced clot lysis than that in the sct-PA induced clot lysis. At the concentration of 3nM of tct-PA, the lysis time of PRP-clot was longer by a factor of 30% in comparison with that of PPP-clot. When the release and the aggregation of platelets were blocked by prostaglandin E1 (PGE1) and theophylline in this experiment, the lysis time of PRP-clot was essentially the same as that of PPP-clot. We then measured the antigen levels of total PAI-1 and t-PA-PAI-1 complex in the lyzed solutions of PRP-clot and PPP-clot to analyse the possible effect of plasminogen activator inhibitor-1 (PAI-1) present in platelets. Most of PAI-1 in a PPP-clot lyzed sample existed as t-PA-PAI-1 complex. In the lyzed solution of PRP-clot, however, the antigen levels of both total PAI-1 and t-PA-PAI-1 complex were significantly higher than those in PPP-clot, and larger amounts of PAI-1 existed as free PAI-1 which possesses activity. These data suggest that at least certain amounts of PAI-1 in platelets exist as an active form and inhibits t-PA activity resulting in the prolongation of the clot lysis time. Activation of platelets, therefore, seems to play an important role in the platelet rich plasma clot lysis induced by t-PA.
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PMID:The potential role of platelet PAl-1 in t-PA mediated clot lysis of platelet rich plasma. 823 58

The effects of the unglycosylated recombinant plasminogen activator BM 06.022, consisting of the kringle 2 and protease domains of tissue-type plasminogen activator (t-PA), on clot lysis were evaluated in an in vitro system. Fresh and aged 125I-labelled human platelet-poor (PPP) and platelet-rich plasma (PRP) and whole blood clots were immersed in human plasma. Clot lysis was quantitated by measurement of released 125I. Fresh PPP clots were time- and concentration-dependently lysed by BM 06.022, alteplase, melanoma t-PA (mt-PA), and urokinase. Fifty per cent clot lysis at 4 h required 3.2-, 6.4- and 15.2-fold higher nM concentrations of mt-PA, BM 06.022, and urokinase respectively compared with alteplase. Maximal lysis (Emax) at 4 h was similar (84.1-87.6%) for BM 06.022, alteplase, and mt-PA, but lower (65.3 +/- 0.6%) for urokinase. Emax for BM 06.022 was lower (P < 0.05) than for alteplase for fresh and aged PRP and whole blood clot lysis. These data suggest that in vitro BM 06.022 achieved, compared with alteplase, the same maximal efficacy in fresh PPP-clot lysis despite a lower potency, but was less effective in lysing aged and fresh PRP and whole blood clots.
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PMID:Differential fibrinolytic properties of the recombinant plasminogen activator BM 06.022 in human plasma and blood clot systems in vitro. 838 40

Anticoagulants have been shown to stimulate fibrinolysis principally via inhibition of thrombin-mediated activation of TAFI (thrombin activatable fibrinolysis inhibitor). Their profibrinolytic effect, however, may vary according to their mechanism of action and to the clot composition. We compared the fibrinolytic activity of the direct thrombin inhibitor melagatran with that of unfractionated heparin in platelet-poor (PPP) and platelet-rich (PRP) models consisting of tissue-factor-induced clots exposed to exogenous t-PA (25 ng/ml). In the PPP clot model, both heparin (0.1-0.6 U/ml) and melagatran (20-320 ng/ml) caused a concentration-dependent shortening of lysis time. However, when drug profibrinolytic activity (lysis ratio) was expressed in function of the aPTT prolongation (aPTT ratio), melagatran was more efficient than heparin. In the PRP clot model, melagatran displayed a fibrinolytic activity fairly comparable to that observed in PPP whilst heparin caused a modest reduction of lysis time only at the highest concentrations. Assay of thrombin and TAFIa generation in defibrinated plasma showed that the presence of platelets markedly reduced the ability of heparin, but not that of melagatran, to inhibit the formation of these enzymes. Altogether these data indicate that melagatran is more efficient than heparin in promoting fibrinolysis, particularly in plateletrich clots, and may thus grant a greater antithrombotic activity by enhancing thrombus dissolution.
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PMID:Profibrinolytic activity of the direct thrombin inhibitor melagatran and unfractionated heparin in platelet-poor and platelet-rich clots. 1806 15