Inhibition of accelerated graft arteriosclerosis by gene transfer of soluble fibroblast growth factor receptor-1 in rat aortic transplants

Wensheng Luo, Ailian Liu, Yong Chen, Hyung M. Lim, Jennifer Marshall-Neff, James H. Black, William Baldwin, Ralph H. Hruban, Susan C. Stevenson, Peter Mouton, Alan Dardik, Barbara J. Ballermann

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1081-1086
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number6
DOIs
StatePublished - Jun 2004

Keywords

  • Chronic rejection
  • Neointima
  • Transplant vasculopathy
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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