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  • Title: Local injection of deferoxamine improves neovascularization in ischemic diabetic random flap by increasing HIF-1α and VEGF expression.
    Author: Wang C, Cai Y, Zhang Y, Xiong Z, Li G, Cui L.
    Journal: PLoS One; 2014; 9(6):e100818. PubMed ID: 24963878.
    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.
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