Details

Autor(en) / Beteiligte

• Crikis, S.
• Zhang, X. M.
• Dezfouli, S.
• Dwyer, K. M.
• Murray‐Segal, L. M.
• Salvaris, E.
• Selan, C.
• Robson, S. C.
• Nandurkar, H. H.
• Cowan, P. J.
• D’Apice, A. J. F.

Titel

Antiinflammatory and Anticoagulant Effects of Transgenic Expression of Human Thrombomodulin in Mice

Ist Teil von

• American journal of transplantation, 2010-02, Vol.10 (2), p.242-250

Ort / Verlag

Malden, USA: Blackwell Publishing Inc

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. Transgenic expression in mice of hTBM results in an antocoagulant and anti‐inflammatory phenotype that confers survival advantages in models of transplantation, thrombosis and pulmonary embolism.