Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein C reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation

Journal of Clinical Investigation

Volumn 101, Issue 3, 1998, Pages 667-676

  Gresele, Paolo ^a   Momi, Stefania ^a   Berrettini, Mauro ^a   Nenci, Giuseppe G ^a   Schwarz, Hans P ^b   Semeraro, Nicola ^c   Colucci, Mario ^c  

^a UNIVERSITY OF PERUGIA   (Italy)

^b Imumno AG   (Austria)

^c UNIVERSITY OF BARI   (Italy)

Author keywords

Bleeding time; Coagulation activation; Fibrinolysis; Protein S; Vessel occlusion

Indexed keywords

ACTIVATED PROTEIN C; THROMBIN;

ANIMAL MODEL; ARTICLE; BLEEDING TIME; FIBRIN FORMATION; FIBRINOLYSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; THROMBOEMBOLISM; THROMBOGENESIS;

EID: 0032005738     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI575     Document Type: Article

References (48)

1. Rapaport, S.I., and L.V.M. Rao. 1992. Initiation and regulation of tissue factor-dependent blood coagulation. Arterioscler. Thromb. 12:1111-1121.
2. Gailani, D., and G.J. Broze. 1991. Factor XI activation in a revised model of blood coagulation. Science. 253:909-912.
3. Warn-Cramer, B.J., and S.I. Rapaport. 1995. Evidence suggestive of activation of the intrinsic pathway of blood coagulation after injection of FXa/phospholipid into rabbits. Arterioscler. Thromb. Vasc. Biol. 15:133-139.
4. Esmon, C.T. 1992. The protein C anticoagulant pathway. Arterioscler. Thromb. 12:135-145.
5. Esmon, C.T., and H.P. Schwarz. 1995. An update on clinical and basic aspects of the protein C anticoagulant pathway. Trends Cardiovasc. Med. 5:141-146.
6. Lane, D.A., P.M. Mannucci, K.A. Bauer, R.M. Bertina, N.P. Bochkov, V. Boulyjenkov, M. Chandy, B. Dahlback, E.K. Ginter, J.P. Miletich, et al. 1996. Inherited thrombophilia: Part 1. Thromb. Haemost. 76:651-662.
7. Dahlback, B., M. Carlsson, and P.J. Svensson. 1993. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc. Nutl. Acad. Sci. USA. 90:1004-1008.
8. Bertina, R.M., B.P.C. Koeleman, T. Koster, F.R. Rosendaal, R.J. Dirven., H. de Ronde, P. van der Veiden, and P.H. Reltsma. 1994. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 369:64-67.
9. Gruber, A., J.H. Griffin, L.A. Harker, and S.R Hanson. 1989. Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model. Blood. 73:639-642.
10. Yamashita, T., A. Matsuoka, A. Funatsu, and J. Yamamoto. 1994. The antithrombotic effect of human activated protein C on He-Ne laser-induced thrombosis in rat mesenteric microvessels. Thromb. Res. 75:33-40.
11. Taylor, F.B., Jr., A. Chang, C.T. Esmon, A. D'Angelo, S. Viganò-D' Angelo, and K.E. Blick. 1987. Protein C prevents the coagulopathic effects of Escherichia coli infusion in the baboon. J. Clin. Invest. 79:918-925.
12. Okajima, K., S. Koga, M. Kaji, M. Inoue, T. Nakagaki, A. Funatsu, H. Okabe, K. Takatsuki, and N. Aoki. 1990. Effect of protein C and activated protein C on coagulation and fibrinolysis in normal human subjects. Thromb. Haemost. 63:48-53.
13. Okajima, K., H. Imamura, S. Koga, M. Inoue, K. Takatsuki, and N. Aoki. 1990. Treatment of patients with disseminated intravascular coagulation by protein C. Am. J. Cardiol. 33:277-278.
14. Comp, P.C., and C.T. Esmon. 1981. Generation of fibrinolytic activity by infusion of activated protein C into dogs. J. Clin. Invest. 68:1221-1228.
15. Burdick, M.D., and R.G. Schaub. 1987. Human protein C induces anticoagulation and increased fibrinolytic activity in the cat. Thromb. Res. 45:413-119.
16. Colucci, M., J.M. Stassen, and D. Collen. 1984. Influence of protein C activation on blood coagulation and fibrinolysis. J. Clin. Invest. 74:200-204.
17. Colucci, M., R. Triggiani, L.G. Cavallo, and N. Semeraro. 1989. Thrombin infusion in endotoxin-treated rabbits reduces the plasma levels of plasminogen activator inhibitor. Evidence for a protein C-mediated mechanism. Blood. 74:1976-1982.
18. Colucci, M., S. Momi, N. Nasimi, G.G. Nenci, N. Semeraro, and P. Gresele. 1995. Activated human protein C (APC) reduces the plasma levels of type 1 plasminogen activator inhibitor (PAI-1) activity in mice. Thromb. Haemost. 73: 1351. (Abstr.)
19. Krishnamurti, C., G.D. Young, C.F. Barr, A. Colleton, and B.M. Alving. 1991. Enhancement of tissue plasminogen activator-induced fibrinolysis by activated protein C in endotoxin-trealed rabbits. J. Lab. Clin. Med. 118:523-530.
20. Bajzar, L., J.C. Fredenburgh, and M.E. Nesheim. 1990. The activated protein C-mediated enhancement of tissue-type plasminogen activator-induced fibrinolysis in a cell-free system. J. Biol. Chem. 265:16948-16954.
21. de Fouw, N.J., F. Haverkate, and R.M. Bertina. 1990. Protein C and fibrinolysis: a link between coagulation and fibrinolysis. Adv. Exp. Med. Biol. 281:235-243.
22. Gruber, A., E. Mori, G.J. del Zoppo, L. Waxman, and J.H. Griffin. 1994. Alteration of fibrin network by activated protein C. Blood. 83:2541-2548.
23. Sakata, Y., and N. Aoki. 1980. Cross-linking of α2-plasmin inhibitor to fibrin by fibrin-stabilizing factor. J. Clin. Invest. 65:290-297.
24. Bajzar, L., J. Morser, and M.E. Nesheim. 1996. TAFI, or plasma procarboxypeptidase B. couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. J. Biol. Chem. 271:16603-16608.
25. Sakharov, D.V., E.F. Plow, and D.C. Rijken. 1997. On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B. J. Biol. Chem. 272: 14477-14482.
26. Bajzar, L., M.E. Nesheim, and P.B. Tracy. 1996. The profibrinolylic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood. 88:2093-2100.
27. Kumada, T., W.A. Dittman, and P.W. Majerus. 1988. A role for thrombomodulin in the pathogenesis of thrombin-induced thromboembolism in mice. Blood. 71:728-733.
28. Komakazu, G., M. Zushi, G. Honda, S. Kawahara, O. Matsuzaki, T. Kanabayashi, S. Yamamoto, I. Maruyama, and K. Suzuki. 1990. Antithrombotic effect of recombinant human thrombomodulin on thrombin-induced thrombembolism in mice. Blood. 75:1396-1399.
29. Paul, W., P. Gresele, S. Momi, G. Bianchi, and C.P. Page. 1993. The eftect of defibrotide on thromboembolism in the pulmonary vasculature of mice and rabbits and in the cerebral vasculature of rabbits. Br. J. Pharmacol. 110: 1565-1571.
30. Momi, S., G.G. Nenci, and P. Gresele. 1992. Thrombin-induced thromboembolism in mice: a model for testing antithrombotic agents acting on coagulation/fibrinolysis. Thromb. Res. 65:S162. (Abstr.)
31. Gresele, P., M. Nasimi, and G.G. Nenci. 1994. Comparison between PEG-Hirudin (PEG-hir) and unfractionated heparin (UFH) in a thrombin-induced pulmonary thromboembolism model in mice. Haemostasis. 24(Suppl.1): 260. (Abstr.)
32. Dreyfus, M., M. Masterson, M. David, G.E. Rivard, F.-M. Muller, W. Kreuz, T. Beeg, A. Minford, J. Hallgrove, J.D. Cohen, et al. 1995. Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency. Semin. Thromb. Hemost. 21: 371-381.
33. Varadi, K., A. Philapitsch, T. Santa, and H.P. Schwarz. 1994. Activation and inactivation of human protein C by plasmin. Thromb. Haemost. 71:615-621.
34. Gresele, P., C. Corona, P. Alberti, and G.G. Nenci. 1990. Picotamide protects mice from death in a pulmonary embolism model by a mechanism independent from thromboxane suppression. Thromb. Haemost. 64:80-86.
35. Di Minno, G., and J.M. Silver. 1983. Mouse antithrombotic assay: a simple method for the evaluation of antithrombotic agents in vivo. Potentiation of antithrombotic activity by ethyl alcohol. J. Pharmacol. Exp. Ther. 225:57-60.
36. Everson Pearse, A.G. 1968. Histochemistry. Theoretical and Applied. Vol. 1. Churchill Livingstone, London. 759 pp.
37. Dejana, E., S. Villa, and G. de Gaetano. 1982. Bleeding time in rats: a comparison of different experimental conditions. Thromb. Haemost. 48:108-111.
38. Declerck, PJ., M. Verstreken, and D. Collen. 1995. Immunoassay of murine t-PA, u-PA and PAI-1 using monoclonal antibodies raised in gene-inactivated mice. Thromb. Haemost. 74:1305-1309.
39. 125 I-fibrin solid-phase fibrinolytic assay for plasmin. Blood. 46:543-553.
40. van Giezen, J.J., J.E. Chung-A-Hing, C.B. Vegter, B.N. Bouma, and J.W. Jansen. 1994. Fibrinolytic activity in blood is distributed over a cellular and the plasma fraction which can be modulated separately. Thromb. Haemost. 72: 887-892.
41. Gruber, A., and J.H. Griffin. 1992. Direct detection of activated protein C in blood from human subjects. Blood. 79:2340-2348.
42. Sakata, Y., D.J. Loskutoff, C.L. Gladson, C.M. Hekman. and J.H. Griffin. 1986. Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor. Blood. 68:1218-1223.
43. von dem Borne, P.A.K., J.C.M. Meijers, and B.N. Bouma. 1995. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood. 86:3035-3042.
44. von dem Borne, P.A.K., L. Bajzar, J.C.M. Meijers, M.E. Nesheim, and B.N. Bouma. 1997. Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. J. Clin. Invest. 99:2323-2327.
45. Rabiet. M.J., J.L. Plantier, and E. Dejana. 1994. Thrombin-induced endothelial cell dysfunction. Br. Med. Bull 50:936-945.
46. Griendling, K.K., and R.W. Alexander. 1996. Endothelial control of the cardiovascular system: recent advances. FASEB (Fed. Am. Soc. Exp. Biol.) J. 10:283-292.
47. Uchiba, M., K. Okajima, K. Murakami, K. Naua, H. Okabe, and K. Takatsuki. 1995. Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats. Thromb. Haemost. 74:1265-1270.
48. Esmon, C.T., F.B. Taylor, Jr., and T.R. Snow. 1991. Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C. Thromb. Haemost. 66:160-165.