Keil, Laura and Schaub, Anna-Lena and Hirt, Stephan W. and Schmid, Christof and Lehle, Karla and von Suesskind-Schwendi, Marietta (2019) Synergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats. HISTOLOGY AND HISTOPATHOLOGY, 34 (7). pp. 821-834. ISSN 0213-3911, 1699-5848
Full text not available from this repository. (Request a copy)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 the RTKIs 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; OBLITERATIVE BRONCHIOLITIS; ANIMAL-MODELS; TGF-BETA; INHIBITION; PATHWAY; HEART; TARGET; Chronic lung allograft dysfunction; Bronchiolitis obliterans; Vatalanib; Imatinib; Everolimus |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 07:15 |
| Last Modified: | 06 Apr 2020 07:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26798 |
Actions (login required)
 |
View Item |
