Restoration of thrombolytic potential in plasminogen-deficient mice by bolus administration of plasminogen
| Autor: | Peter Carmeliet, H.R. Lijnen, D. Collen, Lieve Moons, EF Plow, Ann Bouché, V. A. Ploplis |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Pathology
medicine.medical_specialty Lung Lysis biology business.industry Ratón medicine.medical_treatment Immunology Cell Biology Hematology Pharmacology medicine.disease Biochemistry Tissue plasminogen activator Fibrin medicine.anatomical_structure Pharmacokinetics Fibrinolysis Coagulopathy medicine biology.protein business medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v88.3.870.870 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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