The Potential Mechanism for the Effect of Heparin on Tissue Plasminogen Activator–Mediated Plasminogen Activation
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- 作者：Liang ; Jun F. ; et. al.
- 关键词：Plasminogen activation ; Tissue plasminogen activator ; Heparin stimulation ; Fibrin(ogen) ; Template-type stimulation ; tPA ; tissue plasminogen activator ;
-ACA ; - 刊名：Thrombosis Research
- 出版年：2000
- 出版时间：March 1, 2000
- 年：2000
- 卷：97
- 期：5
- 页码：349-358
- 全文大小：211 K
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文摘
The effects and possible role of heparin on tissue plasminogen activator–mediated plasminogen activation was thoroughly investigated. Direct analysis by sodium dodecyl sulfate–polyacrylamide gel electrophoresis demonstrated that heparin increased the conversion of plasminogen to plasmin. Experiments by florescence quenching suggested that the stimulation of tissue plasminogen activator activity probably was due to a direct binding of heparin to tissue plasminogen activator, causing a conformational change of tissue plasminogen activator and rendering it more accessible to plasminogen interaction. The absence of additive stimulation effects on tissue plasminogen activator–mediated plasminogen activation when both heparin and fibrinogen were present also implied that both compounds interacted with tissue plasminogen activator via the same domain; it appeared to be most likely via the kringle-2 domain in tissue plasminogen activator based on studies using -aminocaproic acid as an inhibitor. Unlike heparin-induced stimulation of antithrombin–thrombin interaction, the heparin-induced stimulation of tissue plasminogen activator did not seem to follow a template model. Only in the presence of a high plasminogen or a low tissue plasminogen activator concentration, massive stimulation of tissue plasminogen activator activity was observed via a pseudotemplate model. The results suggest that precautions concerning high heparin dose should be given during its conjunctive clinical use with tissue plasminogen activator in thrombolytic therapy to reduce the risk of hemorrhage. Publisher: Elsevier Science Language of Publication: English Item Identifier: S0049-3848(99)00188-7 Publication Type: Article ISSN: 0049-3848 Cited by: Sakai, Tokiko; Kyogashima, Mamoru; Kariya, Yutaka; Urano, Tetsumei; Takada, Yumiko; Takada, Akikazu,""Importance of GlcUAb1-3GalNAc(4S,6S) in chondroitin sulfate E for t-PA- and u-PA-mediated Glu-plasminogen activation""Thrombosis Research2000pp. 557-565
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-aminocaproic acid as an inhibitor. Unlike heparin-induced stimulation of antithrombin–thrombin interaction, the heparin-induced stimulation of tissue plasminogen activator did not seem to follow a template model. Only in the presence of a high plasminogen or a low tissue plasminogen activator concentration, massive stimulation of tissue plasminogen activator activity was observed via a pseudotemplate model. The results suggest that precautions concerning high heparin dose should be given during its conjunctive clinical use with tissue plasminogen activator in thrombolytic therapy to reduce the risk of hemorrhage. - Liang, Jun Feng; Park, Yoon Jeong; Song, Hui; Li, Yong Tao; Yang, Victor Chi-Min,""ATTEMPTS: A heparin/protamine-based prodrug approach for delivery of thrombolytic drugs""Journal of Controlled Release2001pp. 145-156
Bibliographic PageFull Text - Park, Yoon-Jeong; Liang, Jun-Feng; Song, Hui; Li, Yong Tao; Naik, Sarita; Yang, Victor C.,""ATTEMPTS: a heparin/protamine-based triggered release system for the delivery of enzyme drugs without associated side-effects""Advanced Drug Delivery Reviews2003pp. 251-265
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