Insight into the profibrinolytic activity of heparin: effects on the activation of plasminogen mediated by urokinase

G.E.BERTOLESI,; E.F.FARÍAS,; D.F.ALONSO,; E.BAL DE KIER JOFFÉ,; L.S.LAURIA DE CIDRE,; A.M.EIJÁN

BLOOD COAGULATION & FIBRINOLYSIS : AN INTERNATIONAL JOURNAL IN HAEMOSTASIS AND THROMBOSIS.

LIPPINCOTT WILLIAMS & WILKINS

Año: 1997 vol. 8 p. 403 - 410

0957-5235

19. Blood Coagul Fibrinolysis. 1997 Oct;8(7):403-10. Insight into the profibrinolytic activity of heparin: effects on the activation of plasminogen mediated by urokinase. Bertolesi GE, Farías EF, Alonso DF, Bal de Kier Joffé E, Lauría de Cidre S, EijánAM. Institute of Oncology, Angel H. Roffo, University of Buenos Aires, Argentina.gabrielb@adhes.uba.ar The aim of this work was to clarify the role of urokinase-type plasminogenactivator (uPA) on the profibrinolytic activity of heparin, chemically modifiedheparins [partially: N-desulfated (N-des), N-desulfated N-acetylated (N-desN-ac), O-desulfated (O-des), O/N-desulfated N-acetylated (O/N-des N-ac)] andheparan sulfate. Binding competition assays of plasminogen and uPA toheparin-sepharose demonstrated that heparin bound to both enzymes. Moreover, inthe presence of increasing amounts of heparin, plasminogen activation mediated byuPA occurred as a bell-shaped curve, suggesting the formation of a ternarycomplex. In contrast, all chemically-modified heparins lacked this cofactoractivity, although N-des and heparan sulfate partially retained the uPA bindingcapacity, and O-des partially bound to both plasminogen and uPA. Plasmaticeuglobulins from mice treated with heparin, as well as with modified heparinswith uPA binding capacity, presented a 2-fold enhancement of 47 kDa lytic band,as assessed by zymographic analysis. Western blotting analysis anti-uPA (47 kDa) showed that the enhanced uPA activity correlated with a true increase in uPAprotein levels. These results suggest that the profibrinolytic activity ofheparin mediated by uPA could be caused by an increase in uPA protein levelsrather than by a cofactor activity mediated by a formation of ternary complexes.  PMID: 9391721 [PubMed - indexed for MEDLINE]