title: Combined administration of naked DNA vectors encoding VEGF and bFGF enhances tissue perfusion and arteriogenesis in ischemic hindlimb.
abstract: Few studies have examined in detail the combined effects of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene delivery on collateral development. Here, we evaluated the potential synergism of naked DNA vectors encoding VEGF and bFGF using a skeletal-muscle based ex vivo angiogenesis assay and compared tissue perfusion and limb loss in a murine model of hindlimb ischemia. In the ex vivo angiogenesis assay, the VEGF+bFGF combination group had a larger capillary sprouting area than those of the LacZ, VEGF, and bFGF groups. Consistent with these results, regional blood flow recovery on day 14 was also highest in the VEGF+bFGF combination group, followed by the bFGF, VEGF, and LacZ groups. The limb loss frequency was 0% in the combination group, whereas the limb loss frequencies of the other groups were 7-29%. The ischemic muscles of the combination group revealed evidence of increased angiogenesis and arteriogenesis and the upregulated expression of genes that may be associated with arteriogenesis, such as those for cardiac ankyrin repeat protein, early growth response factor-1, and transforming growth factor-beta1. Our study has implications for the development of a combined gene therapy for the vascular occlusive diseases.
authors.affiliation: Cardiac and Vascular Center, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Koung Li
authors.initials: KL
authors.lastname: Kim
authors.forename: Hyung-Suk
authors.initials: HS
authors.lastname: Jang
authors.forename: In-Soon
authors.initials: IS
authors.lastname: Shin
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.forename: Jonghoe
authors.initials: J
authors.lastname: Byun
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001158:Arteries / Q000254:growth & development*; D001483:Base Sequence; D004247:DNA / Q000008:administration & dosage*; D017931:DNA Primers; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005822:Genetic Vectors; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004247:DNA