on April 8, 2004
Published online before print April 8, 2004, doi: 10.1161/01.ATV.0000128201.65443.ea
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Submitted on January 19, 2004
Accepted on March 17, 2004
Inhibition of Accelerated Graft Arteriosclerosis by Gene Transfer of Soluble Fibroblast Growth Factor Receptor-1 in Rat Aortic Transplants
Wensheng Luo ;
From the Departments of Medicine (W.L., A.L., H.M.L., B.J.B.), Pathology (Y.C., W.B. III, R.H.H., P.M., B.J.B.), and Surgery (J.H.B., A.D.), Johns Hopkins University School of Medicine, Baltimore, Md.; Department of Medicine (B.J.B.), Albert Einstein College of Medicine, Bronx, NY; and Genetic Therapy Inc. (A Novartis Company) (J.M.-N., S.C.S.), Gaithersburg, Md.
* To whom correspondence should be addressed. E-mail: barbara.ballermann{at}ualberta.ca.
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.
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