Publication: Synergism of imatinib mesylate and everolimus in
attenuation of bronchiolitis obliterans after rat LTX
Authors
Suesskind-Schwendi, M. von ; Valenti, Verena ; Haneya, Assad ; Pühler, T. ; Bewig, B. ; Schmid, C. ; Hirt, S.W. ; Lehle, K.
item.page.secondaryauthor
item.page.director
Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Bronchiolitis obliterans (BO) is a progressive
and fatal disease after lung transplantation (LTX).
Dysregulated growth factor-induced proliferation of
myofibroblasts seems to be responsible for the
development of BO. The aim was to confirm the efficacy
of both inhibitors of receptor tyrosine kinases (RTKI)
and of mammalian target of rapamycin (mTORI) after
rat LTX. We used a rat model of left lung allotransplantation
(F344-to-WKY) to evaluate the effect of
imatinib (RTKI; 20 mg/kg/day; postoperative day (POD)
0-100) alone or in combination with everolimus
(mTORI; 2.5 mg/kg/day; POD 14-100). Non-treated
animals were the reference.
In non-treated rats, acute rejection (AR) peaked
between POD 20 and 30 (19/19) and ended in chronic
rejection (CR) on POD 60/100 (12/12). Imatinib alone
did not prevent AR (6/6), but attenuated the degree of
degenerated bronchioles on POD 30 (non-treated, 57%;
imatinib, 4%), and increased the allografts free of CR on
POD 60/100 (3/12). A combination of imatinib and
everolimus significantly reduced AR, attenuated fibrotic
degenerated bronchioles (5%) and vessels (non-treated,
24%; combination therapy, 11%) on POD 30, and
reduced fibrotic degenerated vessels (non-treated, 97%;
combination therapy, 43%) and bronchioles (non-treated,
88%; combination therapy, 34%) on POD 60/100. Fifty
percent of the animals were completely free of BO and
vasculopathy. In conclusion, co-application of RTKI and
mTORI attenuated the development of BO and
vasculopathy. Thus, imatinib might be an interesting
therapeutic approach after LTX.
publication.page.subject
Citation
Histology and Histopathology, vol. 28, nº 10 (2013)
item.page.embargo
Ir a Estadísticas
Sin licencia Creative Commons.