Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis
| Autor: | Mark Aronovitz, Alexander C. Liu, Barbara C. Furie, Bruce Furie, Richard M. Lawn, Theresa M. Palabrica |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
Antifibrinolytic Apolipoprotein B medicine.drug_class medicine.medical_treatment Transgene Mice Transgenic Apoprotein(a) Tissue plasminogen activator General Biochemistry Genetics and Molecular Biology Mice In vivo Internal medicine Fibrinolysis medicine Animals Humans Radionuclide Imaging biology business.industry Thrombosis General Medicine Lipoprotein(a) Apolipoproteins Endocrinology Biochemistry Tissue Plasminogen Activator biology.protein business Ex vivo medicine.drug |
| Zdroj: | Nature Medicine. 1:256-259 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm0395-256 |
| Popis: | The extensive homology between apolipoprotein(a) and plasminogen has led to the hypothesis that the increased risk for atherosclerosis, cardiac disease and stroke associated with elevated levels of apolipoprotein(a) may reflect modulation of fibrinolysis. We have investigated the role of apolipoprotein(a) on clot lysis in transgenic mice expressing the human apolipoprotein(a) gene. These mice develop fatty streak lesions resembling early lesions of human atherosclerosis. Pulmonary emboli were generated in mice by injection, through the right jugular vein, of a human platelet-rich plasma clot radiolabelled with technetium-99m-labelled antifibrin antibodies. Tissue plasminogen activator was introduced continuously via the right jugular vein. Clot lysis, determined by ex vivo imaging, was depressed in mice carrying the apolipoprotein(a) transgene relative to their sex-matched normal littermates. These results directly demonstrate an in vivo effect of apolipoprotein(a) on fibrinolysis, an effect that may contribute to the pathology associated with elevated levels of this protein. |
| Databáze: | OpenAIRE |
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