Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor.
OBJECTIVE
In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels.


METHODS
The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated.


RESULTS
Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF.


CONCLUSIONS
These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.
Kondoh
Keisuke
K
Department of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Koyama
Hiroyuki
H
Miyata
Tetsuro
T
Takato
Tsuyoshi
T
Hamada
Hirohumi
H
Shigematsu
Hiroshi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D003097:Collateral Circulation; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006614:Hindlimb / Q000098:blood supply*; D007083:Iliac Artery / Q000000981:diagnostic imaging; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply; D011817:Rabbits; D011859:Radiography; D012039:Regional Blood Flow; D014161:Transduction, Genetic / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2