title: Mimic hypoxia improves angiogenesis in ischaemic random flaps.
abstract: BACKGROUND
  Hypoxia is the original signal to promote angiogenesis in ischaemic tissues. However, hypoxia-induced angiogenesis usually cannot compensate for the ischaemic injury in surgery, resulting in tissue necrosis. Mimic hypoxia may be an option to improve angiogenesis for the purpose of preventing or reducing necrosis. In this study, the authors explored the feasibility of applying hypoxic mimic--deferoxamine (DFO) to the treatment of ischaemic random skin flaps.
  
  
  METHODS
  Ischaemic random skin flap models were developed in 18 nude mice using a cutaneous marking technique. The mice were divided into a DFO-treated group and a control group. Vascular endothelial growth factor (VEGF) protein level, vessel density and flap survival rate were evaluated on the seventh postoperative day. In vitro, both VEGF mRNA expression and protein level were investigated in endothelial cells and fibroblasts under DFO, hypoxia and normoxia conditions. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to study the impact of DFO-induced VEGF up-regulation on endothelial cell viability after severe hypoxia injury.
  
  
  RESULTS
  The flap survival rate, vessel density and VEGF level in the DFO group are significantly higher than in the control group. In vitro, DFO-induced increase in VEGF mRNA expression translated into 2.3- and 5.8-fold increases in VEGF protein secretion in DFO-conditioned media of endothelial cells and fibroblasts, respectively. The MTT assay showed that the cell viability both in the DFO group and in the VEGF group was significantly higher than in the control group.
  
  
  CONCLUSIONS
  VEGF praracrine and autocrine secretion in fibroblasts and in endothelial cells play an important role in DFO-induced angiogenesis, which improves ischaemic flap survival. DFO-induced VEGF autocrine secretion also protects endothelial cells from severe hypoxia injury.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Weng
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Lingling
authors.initials: L
authors.lastname: Sheng
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use*; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D017262:Siderophores; D042461:Vascular Endothelial Growth Factor A; D003676:Deferoxamine