title: Local injection of deferoxamine improves neovascularization in ischemic diabetic random flap by increasing HIF-1α and VEGF expression.
abstract: BACKGROUND
  Although the systemic administration of deferoxamine (DFO) is protective in experimental models of normal ischemic flap and diabetic wound, its effect on diabetic flap ischemia using a local injection remains unknown.
  
  
  OBJECTIVE
  To explore the feasibility of local injection of DFO to improve the survival of ischemic random skin flaps in streptozotocin (STZ)-induced diabetic mice.
  
  
  METHODS
  Ischemic random skin flaps were made in 125 mice. Animals were divided into the DFO-treated (n = 20), PBS-treated (n = 16) and untreated (n = 16) groups. Surviving area, vessel density, and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were evaluated on the seventh day after local injection.
  
  
  RESULTS
  The viability of DFO-treated flap was significantly enhanced, with increased regional blood perfusion and capillary density compared with those in the two control groups. Fluorescence-activated cell sorting (FACS) analysis demonstrated a marked increase in systemic Flk-1+/CD11b- endothelial progenitor cells (EPCs) in DFO-treated mice. Furthermore, the expression of VEGF and HIF-1α was increased not only in diabetic flap tissue, but also in dermal fibroblasts cultured under hyperglycemic and hypoxic conditions.
  
  
  CONCLUSIONS
  Local injection of DFO could exert preventive effects against skin flap necrosis in STZ-induced diabetic mice by elevating the expression of HIF-1α and VEGF, increased EPC mobilization, which all contributed to promote ischemic diabetic flap survival.
authors: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors: Chen
authors: C
authors: Wang
authors: Department of Plastic and Aesthetic Surgery, Changzhou NO.2 People's Hospital, Changzhou, P. R. China.
authors: Yuanyuan
authors: Y
authors: Cai
authors: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors: Yun
authors: Y
authors: Zhang
authors: Department of Plastic Surgery, 1st Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Zhuyou
authors: Z
authors: Xiong
authors: Department of Plastic Surgery, 1st Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P. R. China.
authors: Guangzao
authors: G
authors: Li
authors: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
authors: Lei
authors: L
authors: Cui
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000378:metabolism*; D007267:Injections; D007511:Ischemia; D008297:Male; D051379:Mice; D009336:Necrosis / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000187:drug effects; D013524:Surgical Flaps; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D005947:Glucose; D003676:Deferoxamine; D010100:Oxygen