Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes
| Autor: | Douglas B. Cines, Sandra Medinilla, Juan-Carlos Murciano, Donald Eslin, Vladimir R. Muzykantov, Elena N. Atochina |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Erythrocytes
medicine.medical_treatment Biomedical Engineering Bioengineering Pharmacology Applied Microbiology and Biotechnology Fibrin Mice Drug Delivery Systems Fibrinolytic Agents Fibrinolysis medicine Animals Thrombolytic Therapy Carotid Artery Thrombosis Thrombus Blood Coagulation integumentary system biology business.industry T-plasminogen activator hemic and immune systems medicine.disease Thrombosis Rats Venous thrombosis Treatment Outcome Tissue Plasminogen Activator Injections Intravenous Immunology biology.protein Molecular Medicine Erythrocyte Transfusion Pulmonary Embolism business Plasminogen activator Fibrinolytic agent circulatory and respiratory physiology Biotechnology |
| Zdroj: | Nature Biotechnology. 21:891-896 |
| ISSN: | 1546-1696 1087-0156 |
| Popis: | A fibrinolytic agent consisting of a tissue-type plasminogen activator (tPA) coupled to the surface of red blood cells (RBCs) can dissolve nascent clots from within the clot, in a Trojan horse-like strategy, while having minimal effects on preexisting hemostatic clots or extravascular tissue. After intravenous injection, the fibrinolytic activity of RBC-tPA persisted in the bloodstream at least tenfold longer than did that of free tPA. In a model of venous thrombosis induced by intravenously injected fibrin microemboli aggregating in pulmonary vasculature, soluble tPA lysed pulmonary clots lodged before but not after tPA injection, whereas the converse was true for RBC-tPA. Free tPA failed to lyse occlusive carotid thrombosis whether injected before or after vascular trauma, whereas RBC-tPA circulating before, but not injected after, thrombus formation restored blood flow. This RBC-based drug delivery strategy alters the fibrinolytic profile of tPA, permitting prophylactic fibrinolysis. |
| Databáze: | OpenAIRE |
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