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.
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.
de Paula
Erich V
EV
Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil. erich@unicamp.br
Flores-Nascimento
Mariane Cristina
MC
Arruda
Valder R
VR
Garcia
Rosana A
RA
Ramos
Celso D
CD
Guillaumon
Ana T
AT
Annichino-Bizzacchi
Joyce M
JM
D000818:Animals; D000077214:Becaplermin; D004247:DNA / Q000235:genetics*; D018076:DNA, Complementary / Q000096:biosynthesis; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology
D018076:DNA, Complementary; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D004247:DNA