Circulation, Vol 85, 305-312, Copyright © 1992 by American Heart Association
M Levi, BJ Biemond, AJ van Zonneveld, JW ten Cate and H Pannekoek
BACKGROUND. We investigated the effect of inhibition of plasminogen
activator inhibitor-1 (PAI-1) activity by a murine monoclonal anti- human
PAI-1 antibody (MAI-12) on in vitro thrombolysis and on in vivo
thrombolysis and thrombus extension in an experimental animal model for
thrombosis. METHODS AND RESULTS. Thrombolysis, mediated by recombinant
tissue-type plasminogen activator (rt-PA), was studied in an in vitro
system consisting of fibrinogen, plasminogen, and thrombin. Addition of
purified platelets during clot formation inhibited rt-PA-mediated
thrombolysis in a dose-dependent manner. Platelet-dependent thrombolysis
resistance could be completely neutralized by the monoclonal antibody
MAI-12, supporting the notion that the observed resistance is due to PAI-1
released from alpha-granules of platelets. Subsequently, we monitored in
vivo thrombolysis and thrombus extension of human whole blood thrombi that
were allowed to form in rabbit jugular veins. During thrombus formation,
either MAI-12 or an irrelevant antibody was incorporated. Thrombolysis and
thrombus extension were simultaneously measured during endogenous
thrombolysis or upon administration of different dosages of rt-PA. We
observed that endogenous thrombolysis was enhanced in the presence of
MAI-12 compared with the control antibody. Significantly, thrombus
extension was partially prevented by MAI-12 and not by the control antibody
irrespective of whether exogenous rt-PA was systematically administered.
CONCLUSIONS. These observations further confirm the essential role of PAI-1
in the regulation of the thrombolytic system and support the exploration of
adjunctive therapy based on inhibition of PAI-1 activity in thrombolytic
strategies.
ARTICLES
Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis
Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands.
This article has been cited by other articles:
 |
|
 |
|
  B. E. Sobel, D. J. Taatjes, and D. J. Schneider Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis Arterioscler. Thromb. Vasc. Biol., November 1, 2003; 23(11): 1979 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Devaraj, D. Y. Xu, and I. Jialal C-Reactive Protein Increases Plasminogen Activator Inhibitor-1 Expression and Activity in Human Aortic Endothelial Cells: Implications for the Metabolic Syndrome and Atherothrombosis Circulation, January 28, 2003; 107(3): 398 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, T. Shimokawa, H. Yi, K.-i. Isobe, T. Kojima, D. J. Loskutoff, and H. Saito Aging Accelerates Endotoxin-Induced Thrombosis : Increased Responses of Plasminogen Activator Inhibitor-1 and Lipopolysaccharide Signaling with Aging Am. J. Pathol., November 1, 2002; 161(5): 1805 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsuno, O. Kozawa, N. Yoshimi, S. Akamatsu, A. Hara, H. Mori, K. Okada, S. Ueshima, O. Matsuo, and T. Uematsu Lack of alpha 2-antiplasmin promotes pulmonary heart failure via overrelease of VEGF after acute myocardial infarction Blood, September 18, 2002; 100(7): 2487 - 2493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Chavakis, R. A. Pixley, I. Isordia-Salas, R. W. Colman, and K. T. Preissner A Novel Antithrombotic Role for High Molecular Weight Kininogen as Inhibitor of Plasminogen Activator Inhibitor-1 Function J. Biol. Chem., August 30, 2002; 277(36): 32677 - 32682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Podor, D. Singh, P. Chindemi, D. M. Foulon, R. McKelvie, J. I. Weitz, R. Austin, G. Boudreau, and R. Davies Vimentin Exposed on Activated Platelets and Platelet Microparticles Localizes Vitronectin and Plasminogen Activator Inhibitor Complexes on Their Surface J. Biol. Chem., February 22, 2002; 277(9): 7529 - 7539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawasaki, M. Dewerchin, H. R. Lijnen, J. Vermylen, and M. F. Hoylaerts Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice Blood, July 1, 2000; 96(1): 153 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Kohler and P. J. Grant Plasminogen-Activator Inhibitor Type 1 and Coronary Artery Disease N. Engl. J. Med., June 15, 2000; 342(24): 1792 - 1801. [Full Text] [PDF]
|
|
|
|
|
|
S. Madoiwa, N. Komatsu, J. Mimuro, K. Kimura, M. Matsuda, and Y. Sakata Developmental Expression of Plasminogen Activator Inhibitor-1 Associated With Thrombopoietin-Dependent Megakaryocytic Differentiation Blood, July 15, 1999; 94(2): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Farrehi, C. K. Ozaki, P. Carmeliet, and W. P. Fay Regulation of Arterial Thrombolysis by Plasminogen Activator Inhibitor-1 in Mice Circulation, March 17, 1998; 97(10): 1002 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. P. Fay, J. G. Murphy, and W. G. Owen High Concentrations of Active Plasminogen Activator Inhibitor-1 in Porcine Coronary Artery Thrombi Arterioscler. Thromb. Vasc. Biol., October 1, 1996; 16(10): 1277 - 1284. [Abstract] [Full Text]
|
|
|
|
|
|
I. M. Lang and R. R. Schleef Calcium-dependent Stabilization of Type I Plasminogen Activator Inhibitor within Platelet alpha-Granules J. Biol. Chem., February 2, 1996; 271(5): 2754 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Kailasam, R. J. Parmer, J. H. Cervenka, R. A. Wu, M. G. Ziegler, B. P. Kennedy, I. A. Adegbile, and D. T. O'Connor Divergent Effects of Dihydropyridine and Phenylalkylamine Calcium Channel Antagonist Classes on Autonomic Function in Human Hypertension Hypertension, July 1, 1995; 26(1): 143 - 149. [Abstract] [Full Text]
|
|
|
|
|
|
T. K. Nordt, H. Sawa, S. Fujii, and B. E. Sobel Induction of Plasminogen Activator Inhibitor Type-1 (PAI-1) by Proinsulin and Insulin In Vivo Circulation, February 1, 1995; 91(3): 764 - 770. [Abstract] [Full Text]
|
|