|
|
 Previous Article | Table of Contents | Next Article 
Restoration of thrombolytic potential in plasminogen-deficient mice by
bolus administration of plasminogen
HR Lijnen, P Carmeliet, A Bouche, L Moons, VA Ploplis, EF Plow and D Collen
Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Homozygous plasminogen-deficient (Plg-/-) mice had a significantly reduced
thrombolytic capacity toward intravenously injected 125I-fibrin labeled
plasma clots prepared from Plg-/- murine plasma (9% +/- 3% lysis after 8
hours; (mean +/- SEM, n = 6), as compared with 82% +/- 8% in wild-type
mice; P < .0001). Bolus injection of 1 mg purified murine plasminogen in
10- to 17-week-old Plg-/- mice increased the plasminogen antigen and
activity levels at 8 hours to normal levels (130 +/- 5 micrograms/mL).
Plasminogen administration was associated with significant restoration of
thrombolytic potential (64% +/- 7% spontaneous clot lysis; P < .0001
versus lysis without plasminogen injection). Bolus injection of 1 mg
plasminogen in homozygous tissue- type plasminogen activator-deficient
(t-PA-/-) mice doubled the plasminogen antigen and activity levels after 8
hours and increased 125I-fibrin clot lysis at 8 hours from 13% +/- 3% to
34% +/- 5% (P = .008). Fibrinogen, t-PA antigen and alpha 2-antiplasmin
activity levels after 8 hours were not significantly different in the
groups with or without plasminogen injection. Injection of plasminogen
induced a variable increase (on average 7- to 10-fold) of PAI-1, but no
correlation with the extent of spontaneous clot lysis was observed.
Histopathologic examination at the end of the experiments revealed that
fibrin deposition in the liver of Plg-/- mice was slightly reduced 8 hours
after bolus plasminogen injection (P = .007) and markedly reduced after 24
hours (P < .0001). Plasminogen antigen levels in liver extracts were
comparable with those found in wild-type mice at 8 hours (130 +/- 20 versus
110 +/- 15 ng/mg protein) and decreased to 25 +/- 3.2 ng/mg protein at 24
hours. Thus, restoration of normal plasminogen levels in Plg-/- mice
normalized the thrombolytic potential toward experimentally induced
pulmonary emboli, and resulted in removal of endogenous fibrin deposits
within 24 hours.
Volume 88,
Issue 3,
pp. 870-876,
08/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Li, A. Ny, G. Leonardsson, K. S. Nandakumar, R. Holmdahl, and T. Ny
The Plasminogen Activator/Plasmin System Is Essential for Development of the Joint Inflammatory Phase of Collagen Type II-Induced Arthritis
Am. J. Pathol.,
March 1, 2005;
166(3):
783 - 792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Swaisgood, E. L. French, C. Noga, R. H. Simon, and V. A. Ploplis
The Development of Bleomycin-Induced Pulmonary Fibrosis in Mice Deficient for Components of the Fibrinolytic System
Am. J. Pathol.,
July 1, 2000;
157(1):
177 - 187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-l. Chen, J. A. Indyk, T. H. Bugge, K. W. Kombrinck, J. L. Degen, and S. Strickland
Neuronal Death and Blood-Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes
J. Neurosci.,
November 15, 1999;
19(22):
9813 - 9820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.R. Lijnen, K. Okada, O. Matsuo, D. Collen, and M. Dewerchin
alpha 2-Antiplasmin Gene Deficiency in Mice Is Associated With Enhanced Fibrinolytic Potential Without Overt Bleeding
Blood,
April 1, 1999;
93(7):
2274 - 2281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Schott, C.-E. Dempfle, P. Beck, A. Liermann, A. Mohr-Pennert, M. Goldner, P. Mehlem, H. Azuma, V. Schuster, A.-M. Mingers, et al.
Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency
N. Engl. J. Med.,
December 3, 1998;
339(23):
1679 - 1686.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z.-F. Huang, D. Higuchi, N. Lasky, and G. J. Broze Jr
Tissue Factor Pathway Inhibitor Gene Disruption Produces Intrauterine Lethality in Mice
Blood,
August 1, 1997;
90(3):
944 - 951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Schuster, A.-M. Mingers, S. Seidenspinner, Z. Nussgens, T. Pukrop, and H. W. Kreth
Homozygous Mutations in the Plasminogen Gene of Two Unrelated Girls With Ligneous Conjunctivitis
Blood,
August 1, 1997;
90(3):
958 - 966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
