Rosiglitazone attenuates transplant arteriosclerosis after allogeneic aorta transplantation in rats
| Autor: | Flip A. Klatter, Donald R. A. Uges, Jan-Luuk Hillebrands, Geanina Onuta, Jan Rozing, Mark Walther Boer, Jan Freark de Boer, Heleen Rienstra, Anton J.M. Roks, Gerjan Navis |
|---|---|
| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Vascular smooth muscle Arteriosclerosis Rats Inbred WF transplant arteriosclerosis T-Lymphocytes Regulatory Muscle Smooth Vascular rosiglitazone Rats Inbred BN rat Aorta Abdominal IL-2 receptor GENE-EXPRESSION RENAL-TRANSPLANTATION FOXP3 Forkhead Transcription Factors smooth muscle cells medicine.anatomical_structure surgical procedures operative ACTIVATED-RECEPTOR-GAMMA CARDIOVASCULAR-DISEASE PPAR-GAMMA Rosiglitazone Chemokines CXC medicine.drug Neointima medicine.medical_specialty Regulatory T cell T cell Receptor Platelet-Derived Growth Factor beta Transplantation Immunology Internal medicine medicine Animals Transplantation Homologous REGULATORY T-CELLS Cell Proliferation BALLOON INJURY Transplantation business.industry DIABETES-MELLITUS ENDOTHELIAL-CELLS Chemokine CXCL12 Rats VASCULAR SMOOTH-MUSCLE PPAR gamma Endocrinology Rats Inbred Lew Thiazolidinediones business |
| Zdroj: | Transplantation, 84(4), 517-526. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 0041-1337 |
| Popis: | Background. Transplant arteriosclerosis is a leading cause of chronic transplant dysfunction and is characterized by occlusive neointima formation in intragraft arteries. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs and adequate therapy is not available. In this study, we determined the efficacy of the synthetic peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone to attenuate the development of transplant arteriosclerosis in rat aortic allografts.Methods. Lewis aortic allografts were transplanted into Brown Norway recipient rats. Recipient rats received either similar to 5 mg rosiglitazone/day (starting 1 week before transplantation until the end of the experiment) or were left untreated. Transplant arteriosclerosis was quantified using morphometric analysis. Alloreactivity was measured in vitro using mixed lymphocyte reactions. Regulatory T cell frequency and function were analyzed using flow cytometry and in vitro suppression assays, respectively. Intragraft gene expression was analyzed using real-time polymerase chain reaction. Finally, medial and neointimal vascular smooth muscle cell proliferation was analyzed in vitro.Results. Rosiglitazone significantly reduced transplant arteriosclerosis development 8 weeks after transplantation (P Conclusion. PPAR gamma agonists may offer a new therapeutic strategy in clinical transplantation to attenuate the development of transplant arteriosclerosis and thereby chronic transplant dysfunction. |
| Databáze: | OpenAIRE |
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