Platelet-derived growth factor receptor inhibition reduces allograft arteriosclerosis of heart and aorta in cholesterol-fed rabbits
| Autor: | Elisabeth Buchdunger, Jussi Tikkanen, Rainer Krebs, Eva M. Aaltola, Outi Laitinen, Petri Koskinen, Karl B. Lemström, Roope Sihvola |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Platelet-derived growth factor medicine.medical_treatment Hypercholesterolemia Aortic Diseases Antineoplastic Agents Aorta Thoracic Coronary Artery Disease Piperazines Cholesterol Dietary chemistry.chemical_compound medicine.artery Internal medicine medicine Animals Transplantation Homologous Receptors Platelet-Derived Growth Factor Heart transplantation Platelet-Derived Growth Factor Transplantation Aorta biology Vascular disease business.industry Incidence Macrophages Graft Survival Arteriosclerosis medicine.disease Surgery Endocrinology Imatinib mesylate Pyrimidines chemistry Benzamides biology.protein Imatinib Mesylate Heart Transplantation Female Rabbits business Platelet-derived growth factor receptor |
| Zdroj: | Transplantation. 75(3) |
| ISSN: | 0041-1337 |
| Popis: | Background Crosstalk between pro-inflammatory cytokines and platelet-derived growth factor (PDGF) regulates smooth-muscle-cell proliferation in cardiac-allograft arteriosclerosis. In this study, we tested the effect of STI 571, a novel orally active protein tyrosine kinase (PTK) inhibitor selective for PDGF receptor (PDGF-R) on transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. Methods. Cardiac allografts were transplanted heterotopically from Dutch Belted to New Zealand White rabbits. A 0.5% cholesterol diet was begun 4 days before transplantation. Recipients received STI 571 5 mg/kg per day or vehicle intraperitoneally throughout the study period of 6 weeks. Cyclosporine A was given as background immunosuppression. Results. In cardiac allografts of vehicle-treated rabbits, 76.2±2.1% of medium-sized arteries were affected by intimal thickening, and the percentage of arterial occlusion was 45.0±5.0%. Treatment with STI 571 reduced the incidence of affected medium-sized arteries to 41.2±8.1% (P |
| Databáze: | OpenAIRE |
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