Publication: Synergism of imatinib, vatalanib and everolimus in the prevention of chronic lung allograft rejection after lung transplantation (LTx) in rats
Authors
Keil, Laura ; Schaub, Anna Lena ; Hirt, Stephan W. ; Schmid, Christof ; Lehle, Karla ; Suesskind Schwendi, Marietta von
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-18-088
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info:eu-repo/semantics/article
Description
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.
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