Antiinflammatory and Anticoagulant Effects of Transgenic Expression of Human Thrombomodulin in Mice
| Autor: | L M Murray-Segal, X M Zhang, Evelyn J Salvaris, Peter J. Cowan, Shala Dezfouli, Karen M. Dwyer, Carly Selan, Harshal Hanumant Nandurkar, Sandra Crikis, Simon C. Robson, Ajf d'Apice |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Genetically modified mouse
Swine Transgene Xenotransplantation medicine.medical_treatment Thrombomodulin Anti-Inflammatory Agents Mice Transgenic Article Mice medicine Immunology and Allergy Animals Humans Pharmacology (medical) Transgenes Clotting factor Transplantation business.industry medicine.disease Thrombosis Rats Venous thrombosis Disease Models Animal medicine.anatomical_structure Immunology Cyclosporine business Blood vessel |
| Popis: | Thrombomodulin (TBM) is an important vascular anticoagulant that has species specific effects. When expressed as a transgene in pigs, human (h)TBM might abrogate thrombotic manifestations of acute vascular rejection (AVR) that occur when GalT-KO and/or complement regulator transgenic pig organs are transplanted to primates. hTBM transgenic mice were generated and characterized to determine whether this approach might show benefit without the development of deleterious hemorrhagic phenotypes. hTBM mice are viable and are not subject to spontaneous hemorrhage, although they have a prolonged bleeding time. They are resistant to intravenous collagen-induced pulmonary thromboembolism, stasis-induced venous thrombosis and pulmonary embolism. Cardiac grafts from hTBM mice to rats treated with cyclosporine in a model of AVR have prolonged survival compared to controls. hTBM reduced the inflammatory reaction in the vein wall in the stasis-induced thrombosis and mouse-to-rat xenograft models and reduced HMGB1 levels in LPS-treated mice. These results indicate that transgenic expression of hTBM has anticoagulant and antiinflammatory effects that are graft-protective in murine models. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|