title: Enhancement of flap survival and changes in angiogenic gene expression after AAV2-mediated VEGF gene transfer to rat ischemic flaps.
abstract: Necrosis of surgically transferred flaps due to ischemia is a serious wound problem. We evaluated the improvement of flap survival and changes in angiogenic gene expression profiles after transfer of the VEGF gene by means of adeno-associated virus type 2 (AAV2) vector to rat ischemic flaps. Thirty rats were divided into one experimental group, one AAV2-GFP group, and one saline group. AAV2-VEGF or AAV2-GFP were injected intradermally into the rat dorsum in the AAV2-VEGF or AAV2-GFP group. The saline group received saline injection. A 3 × 10 cm flap was raised in each rat two weeks post-injection. One week after surgery, flap viability was evaluated. Angiogenesis real-time PCR array was performed to analyze the expression of angiogenesis-associated genes. The AAV2-VEGF treatment significantly improved flap survival (p<0.05). Immunohistochemical staining showed increased VEGF expression in AAV2-VEGF treated flaps. The PCR array identified remarkable changes in 6 out of the 84 angiogenesis-associated genes in AAV2-VEGF treated flaps. Particularly, EGF, PDGF-A and VEGF-B genes were up-regulated in these flaps. In contrast, FGF2 gene expression was down-regulated. In conclusion, AAV2-VEGF improves flap survival and affects the expression of a series of endogenous growth factor genes, which likely play critical roles in the enhancement of ischemic flap survival.
authors.affiliation: Department of Plastic Surgery, Rhode Island Hospital, Brown University School of Medicine, Providence, USA. wangxt_2000@yahoo.com
authors.forename: Xiao Tian
authors.initials: XT
authors.lastname: Wang
authors.forename: Bella
authors.initials: B
authors.lastname: Avanessian
authors.forename: Qiangzhong
authors.initials: Q
authors.lastname: Ma
authors.forename: Heather
authors.initials: H
authors.lastname: Durfee
authors.forename: Yu Qing
authors.initials: YQ
authors.lastname: Tang
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Liu
mesh_terms: D000818:Animals; D000229:Dependovirus; D015536:Down-Regulation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006085:Graft Survival; D007150:Immunohistochemistry; D007511:Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps / Q000098:blood supply*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D042561:Vascular Endothelial Growth Factor B / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; C075278:platelet-derived growth factor A; C467498:vascular endothelial growth factor A, rat; C467482:vascular endothelial growth factor B, mouse; D016222:Fibroblast Growth Factor 2