Journal
TRANSLATIONAL RESEARCH
Volume 153, Issue 5, Pages 232-239Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.trsl.2009.02.002
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2004-13158-2]
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The protein infusion of basic fibroblast growth factor-2 (FGF-2) and platelet derived growth factor-BB (PDGF-BB) have been shown to promote the formation of a stable and functional vascular network in small and large animal models of ischemia. Here, we sought to determine whether a similar effect could be obtained using a gene-therapy-based strategy with nonviral vectors. Rats underwent a surgical procedure to create hindlimb ischemia and were injected with a combination of plasmids that expressed FGF-2 and PDGF-BB. Anatomical and functional parameters of the angiogenesis and arteriogenesis response were evaluated after 4 weeks. The results were compared with rats injected with plasmids that expressed a reporter gene or the extensively studied vascular endothelial growth factor (VEGF165) alone. Treatment with the FGF-2/PDGF-BB combination increased the angiogenesis and arteriogenesis response compared with the empty plasmid, and it was as effective as VEGF165. In terms of safety, the combination allowed the use of a 50% lower individual dose of each plasmid and in addition promoted the formation of more stable vessels than VEGF165. In conclusion, the dual gene transfer of FGF-2 and PDGF-BB using nonviral vectors is safe and effective in promoting the formation of a functional vascular network in a rodent model of hindlimb ischemia. (Translational Research 2009; 153:232-239)
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