Dual gene transfer of fibroblast growth factor-2 and platelet derived growth factor-BB using plasmid deoxyribonucleic acid promotes effective angiogenesis and arteriogenesis in a rodent model of hindlimb ischemia

Autor(es)

De Paula, Erich V. ^[1] ; Flores-Nascimento, Mariane Cristina ^[2] ; Arruda, Valder R. ^[2] ; Garcia, Rosana A. ^[2] ; Ramos, Celso D. ^[2] ; Guillaumon, Ana T. ^[2] ; Annichino-Bizzacchi, Joyce M. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL RESEARCH; v. 153, n. 5, p. 232-239, MAY 2009.
• Citações Web of Science: 8

Resumo

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) (AU)

• Processo FAPESP: 04/13158-2 - Doença vascular arterial e venosa: fisiopatologia, identificação de novos fatores de risco, e terapia gênica
• Beneficiário: Joyce Maria Annichino-Bizzacchi
• Modalidade de apoio: Auxílio à Pesquisa - Temático