Anticoagulant low molecular weight heparin does not enhance the activation of plasminogen by tissue plasminogen activator.
The activity of tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) is stimulated by heparin. Heparin binds tightly to t-PA, u-PA, and plasminogen and decreases the usual stimulatory effect of fibrin on t-PA activity. In the present study we have found that low molecular weight heparin (LMW-heparin) preparations obtained by nitrous acid depolymerization or heparinase treatment of standard heparin have different properties with respect to their interaction with the fibrinolytic system. LMW-heparin prepared by either method does not stimulate plasmin formation by t-PA. However, these preparations of heparin still efficiently accelerate the inhibition of thrombin by antithrombin III. Binding data show that LMW-heparin does not bind t-PA and Glu-plasminogen and only binds very weakly to Lys-plasminogen. These results illustrate that it is possible to selectively destroy the fibrinolytic stimulating properties of heparin while leaving the classical anticoagulant characteristics intact.
Andrade-Gordon
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P
Department of Molecular Pharmacology, State University of New York, Stony Brook 11794-8651.
Strickland
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S
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D002417:Cattle; D002850:Chromatography, Gel; D006493:Heparin / Q000302:isolation & purification / Q000494:pharmacology*; D019763:Heparin Lyase; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D011133:Polysaccharide-Lyases; D013329:Structure-Activity Relationship; D013552:Swine; D013917:Thrombin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000990:Antithrombin III; D010958:Plasminogen; D006493:Heparin; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase