Low-affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin
Low-affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin
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低亲和力肝素通过凝血酶刺激纤溶酶原激活剂抑制剂-1 失活
DOI：
10.1182/blood.v84.4.1164.bloodjournal8441164
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发表时间：
1994
期刊：
影响因子：
20.3
通讯作者：
M. Schapira
中科院分区：
文献类型：
--
作者：
P. Patston;M. Schapira
The influence of heparin on the reaction between thrombin and plasminogen activator inhibitor-1 (PAI-1) has been examined. With a 50- fold excess of PAI-1, the rate constant for the inhibition of thrombin was 458 mol/L-1s-1, which increased to 5,000 mol/L-1s-1 in the presence of 25 micrograms/mL unfractionated heparin or heparin with low affinity for antithrombin. The effect of low affinity heparin was then examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, using close to equimolar concentrations of reactants. Thrombin and PAI-1 formed a stable stoichiometric complex in the absence of heparin, which did not dissociate after the addition of 25 micrograms/mL low-affinity heparin. In contrast, when low-affinity heparin was added at the beginning of the reaction, there was an initial increase in PAI-1- thrombin complex formation, but this was rapidly followed by substantial proteolytic cleavage of unreacted PAI-1 and of the thrombin- PAI-1 complex. The idea that the relative concentrations of thrombin and PAI-1, and the presence of low affinity heparin, could influence the products of the reaction was examined in detail. Quantitative zymographic analysis of tissue plasminogen activator and PAI-1 activities and chromogenic substrate assay of thrombin activity showed that low-affinity heparin stimulated the inactivation of PAI-1 by an equimolar amount of thrombin, but caused only a minimal stimulation of thrombin inhibition. It is concluded that low-affinity heparin stimulates thrombin inhibition when PAI-1 is in excess, but, unexpectedly, that low-affinity heparin enhances PAI-1 inactivation when thrombin is equimolar to PAI-1.
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影响因子：
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作者：
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DOI：
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DOI：
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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作者：
Owen,J;Friedman,KD;Grossman,BA;Wilkins,C;Berke,AD;Powers,ER
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