P413Human fused protein IO-3 stimulates growth of new vessels

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Abstract

Human fused protein IO-3 contains part of basic fibroblast growth factor (bFGF), and Ig-like domain of fibroblast growth factor receptor 1 (FGFR1). Here, we investigated the potential of IO-3 for therapeutic neovascularization in a modified rabbit hind limb ischemia model (T. Rissanen et al. 2002). New Zealand white rabbits were randomized to receive IO-3, 25 mcg, intramuscularly (N=24) or saline phosphate buffer, intramuscularly (N=24) in hind limb ischemia area. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was used for angiogenesis evaluation. Number of vessels in ischemia area was assessed by immunohistochemistry when rabbits were euthanized. DCE-MRI showed that IO-3 resulted in increases in vascular permeability in muscles 8 days after the injection. In contrast, saline phosphate buffer injected in the ischemia area did not induce acute vascular permeability. Also, injection of IO-3 increased collateral growth and blood flow compared with control. The angiogenesis response consisted of the enlargement of pre-existing as well as increase in capillary density. Immunohistochemically, there was significant increase of number vessels in IO-3 group in comparison with control group (P=0.01). This study demonstrates for the first time that human fused protein IO-3 induces vascular permeability and therapeutic angiogenesis in the area of ischemia and could be investigated for the treatment of vascular diseases.

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