Synergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats.
Histol Histopathol
; 34(7): 821-834, 2019 Jul.
Article
em En
| MEDLINE
| ID: mdl-30706940
ABSTRACT
Chronic lung allograft dysfunction (CLAD) still remains a major drawback in the outcome following lung transplantation (LTx). New therapeutic strategies are warranted. Growth factors and their receptors like platelet-derived growth factor-receptor (PDGFR) and vascular endothelial growth factor-receptor (VEGFR), may play a crucial role in the development of CLAD, especially bronchiolitis obliterans (BO) and vasculopathy. In this study, we used an orthotopic left lung transplantation model from Fischer (F344) to Wystar Kyoto (WKY) rats to investigate the effect of the receptor tyrosine kinase inhibitor (RTKI) vatalanib alone, the dual combination of vatalanib and imatinib and a triple therapy consisting of vatalanib, imatinib and the mammalian target of rapamycin inhibitor (mTORI) everolimus on the development of CLAD after LTx in rats. With this trial we demonstrated that monotherapy with vatalanib attenuated mild and severe chronic vascular rejection, whereas dual therapy (vatalanib and imatinib) after LTx also showed a significant reduction of chronic bronchiolar rejection and interstitial fibrosis. By adding everolimus, the effect of vatalanib and imatinib could additionally be increased. In conclusion, the combination of mTORI and RTKIs might be a possible strategy in the prevention of CLAD and BO.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ftalazinas
/
Piridinas
/
Transplante de Pulmão
/
Inibidores de Proteínas Quinases
/
Mesilato de Imatinib
/
Everolimo
/
Rejeição de Enxerto
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Histol Histopathol
Assunto da revista:
HISTOLOGIA
/
PATOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha