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


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.


CONCLUSIONS
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.
Luo
Wensheng
W
Department of Medicine, Hopkins University School of Medicine, Baltimore, Md, USA.
Liu
Ailian
A
Chen
Yong
Y
Lim
Hyung M
HM
Marshall-Neff
Jennifer
J
Black
James H
JH
Baldwin
William
W
Hruban
Ralph H
RH
Stevenson
Susan C
SC
Mouton
Peter
P
Dardik
Alan
A
Ballermann
Barbara J
BJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012995:Solubility; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology
D018076:DNA, Complementary; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1