Combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis in murine aortic allografts
| Autor: | Stephan M. Ensminger, S. Eckl, Martina Ramsperger-Gleixner, J. Hoffmann, Christian Heim, S. Abele-Ohl, Michael Weyand |
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| Rok vydání: | 2010 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Ticlopidine Platelet Aggregation Arteriosclerosis Pharmacology chemistry.chemical_compound Mice P2Y12 Internal medicine medicine Animals Transplantation Homologous Platelet cardiovascular diseases Aorta Abdominal Everolimus Receptor Sirolimus Transplantation business.industry Antagonist Clopidogrel Mice Inbred C57BL Adenosine diphosphate Disease Models Animal Treatment Outcome chemistry Cardiology Mice Inbred CBA Drug Therapy Combination business Immunosuppressive Agents Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Transplant international : official journal of the European Society for Organ Transplantation. 23(9) |
| ISSN: | 1432-2277 |
| Popis: | Our group has shown that platelet inhibition with clopidogrel, an antagonist of the P2Y12 adenosine diphosphate receptor on platelets, reduced the formation of transplant arteriosclerosis. The aim of this study was to investigate whether a combination of cyclosporin or everolimus with clopidogrel has a beneficial effect on the development of transplant arteriosclerosis. Fully MHC mismatched C57Bl/6 (H2(b)) donor aortas were transplanted into CBA.J (H2(k)) recipients and mice received either clopidogrel alone (1 mg/kg/day) or in combination with cyclosporin (2 mg/kg/day) or everolimus (0.05 mg/kg/day). Grafts were analysed by histology and morphometry on day 30 after transplantation. In mice treated with clopidogrel alone, transplant arteriosclerosis was significantly reduced [intima proliferation 56 +/- 11% vs. 81 +/- 7% (control)/n = 7]. Daily application of everolimus reduced the development of transplant arteriosclerosis compared with untreated controls [intima proliferation of 29 +/- 9% vs. 81 +/- 7% (control)/n = 7]. Strikingly, combination of clopidogrel and everolimus almost abolished the formation of transplant arteriosclerosis [intima proliferation: 11 +/- 8% vs. 81 +/- 7% (control)/n = 7]. By contrast, combination of cyclosporin and clopidogrel compared with clopidogrel alone showed no additive effect. These results demonstrate that combination of platelet- and mammalian target of Rapamycin-inhibition can dramatically reduce the development of transplant arteriosclerosis. |
| Databáze: | OpenAIRE |
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