title: Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation.
abstract: Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective noninvasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by noninvasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the increase in FGF-2 expression with pFGFE+ was sufficient to significantly increase ischemic limb blood flow, measured by laser Doppler perfusion imaging, beginning on postoperative day 3. Ischemic limb blood flow in the pFGFE+ treatment group remained significantly higher than all control groups through the end point of the study, postoperative day 14. Immunohistochemical staining of gastrocnemius cross sections determined there was a twofold increase in capillary density in the pFGFE+ treatment group. Our results suggest that pFGFE+ is a potential noninvasive, nonviral therapeutic approach to increase perfusion and angiogenesis for the treatment of limb ischemia.
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ferraro
authors.forename: Y L
authors.initials: YL
authors.lastname: Cruz
authors.forename: M
authors.initials: M
authors.lastname: Baldwin
authors.forename: D
authors.initials: D
authors.lastname: Coppola
authors.forename: R
authors.initials: R
authors.lastname: Heller
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018274:Electroporation; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000628:therapy; D051381:Rats; D012039:Regional Blood Flow
chemical_list: D016222:Fibroblast Growth Factor 2
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