title: Superior neovascularization and muscle regeneration in ischemic skeletal muscles following VEGF gene transfer by rAAV1 pseudotyped vectors.
abstract: Recombinant adeno-associated virus serotype 2 (rAAV2) vector has been widely employed for gene therapy. Recent progress suggests that the new serotypes of AAV showed a better performance than did AAV2 in normal tissues. Here, we evaluate the potential role of human vascular endothelial growth factor (VEGF) gene transfer using rAAV vector pseudotyped with serotype 1 capsid proteins (rAAV1) in the treatment of muscle ischemia. In ischemic skeletal muscles, the rAAV1-LacZ vector allowed higher level, broader distribution, and long-lasting gene expression compared with the rAAV2-LacZ vector. Muscle VEGF165 production following the rAAV1-VEGF165 vector injection was 5-10 times higher than that following the rAAV2-VEGF165 vector injection. VEGF165 production mediated by the rAAV1-VEGF165 vector stimulated a large set of neovascularization with relatively mature vascular structures and enhanced muscle regeneration in the ischemic skeletal muscles. Thus, the rAAV1-VEGF165 vector mediated gene transfer may be a therapeutic approach to peripheral vascular diseases.
authors.affiliation: Department of Cardiology, Peking University Third Hospital, No. 49, North Garden Road, Beijing 100083, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jianwei
authors.initials: J
authors.lastname: Tian
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018014:Gene Transfer Techniques; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011995:Recombination, Genetic; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A