TY - JOUR
T1 - Inhibition of accelerated graft arteriosclerosis by gene transfer of soluble fibroblast growth factor receptor-1 in rat aortic transplants
AU - Luo, Wensheng
AU - Liu, Ailian
AU - Chen, Yong
AU - Lim, Hyung M.
AU - Marshall-Neff, Jennifer
AU - Black, James H.
AU - Baldwin, William
AU - Hruban, Ralph H.
AU - Stevenson, Susan C.
AU - Mouton, Peter
AU - Dardik, Alan
AU - Ballermann, Barbara J.
PY - 2004/6
Y1 - 2004/6
N2 - Objective-Because increased fibroblast growth factor-1 (FGF-1) and FGF receptor (FGFR) expression correlate with the development of accelerated graft arteriosclerosis in transplanted human hearts, this study sought to determine whether local gene transfer of soluble FGFR-1, capable of binding both FGF-1 and FGF-2, could blunt the development of accelerated graft arteriosclerosis in the rat aortic transplant model. Methods and Results-A construct encoding the FGFR-1 ectodomain, capable of neutralizing FGF-2 action, was expressed in rat aortic allografts, using adenoviral gene transfer at the time of transplantation. Neointima formation was inhibited in aortic allografts transduced with soluble FGFR-1, compared with allografts transduced with Null virus. Conclusion-FGFs play a causal role in the development of accelerated graft arteriosclerosis in the rat aortic transplant model. Targeted interruption of FGF function could potentially reduce neointima formation in patients with heart and kidney transplants.
AB - Objective-Because increased fibroblast growth factor-1 (FGF-1) and FGF receptor (FGFR) expression correlate with the development of accelerated graft arteriosclerosis in transplanted human hearts, this study sought to determine whether local gene transfer of soluble FGFR-1, capable of binding both FGF-1 and FGF-2, could blunt the development of accelerated graft arteriosclerosis in the rat aortic transplant model. Methods and Results-A construct encoding the FGFR-1 ectodomain, capable of neutralizing FGF-2 action, was expressed in rat aortic allografts, using adenoviral gene transfer at the time of transplantation. Neointima formation was inhibited in aortic allografts transduced with soluble FGFR-1, compared with allografts transduced with Null virus. Conclusion-FGFs play a causal role in the development of accelerated graft arteriosclerosis in the rat aortic transplant model. Targeted interruption of FGF function could potentially reduce neointima formation in patients with heart and kidney transplants.
KW - Chronic rejection
KW - Neointima
KW - Transplant vasculopathy
KW - Transplantation
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U2 - 10.1161/01.ATV.0000128201.65443.ea
DO - 10.1161/01.ATV.0000128201.65443.ea
M3 - Article
C2 - 15072997
AN - SCOPUS:2942511346
SN - 1079-5642
VL - 24
SP - 1081
EP - 1086
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 6
ER -