© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor
aDepartment of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
bDivision of Tissue Engineering, The University of Tokyo Hospital, Tokyo, Japan
cDivision of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8655, Japan
dDepartment of Molecular Medicine, Sapporo Medical University, Sapporo, Japan
* Corresponding author. Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8655, Japan. Tel.: +81-3-5800-8653; fax: +81-3-3811-6822. hkoyama-tky{at}umin.ac.jp
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. Method: 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 β-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5 x 106 cells), and the next day, a pair of specifically infected fibroblasts (total 1 x 107 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. Conclusion: 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.
KEYWORDS Vascular endothelial growth factor; Basic fibroblast growth factor; Therapeutic angiogenesis; Arteriogenesis; Ex vivo gene transfer; Collateral vessels
Time for primary review 24 days
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