title: Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival.
abstract: BACKGROUND
  The local skin flap procedure is very useful for reconstruction. However, flap necrosis caused by circulatory failure can occur at its distal portion. Hypoxia-inducible factors (HIFs) in endothelial cells (ECs) help to maintain ECs and promote vascularization, and HIF-2α is abundantly expressed in ECs. However, the mechanisms of action of HIF-2α in ECs are not yet fully understood. The aim of this study was to evaluate the in vivo effects of overexpression of HIF-2α in ECs on skin flap survival.
  
  
  METHODS
  A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of transgenic mice (Tg mice) with EC-specific HIF-2α conditional overexpression and wild-type littermate control mice (n = 6). Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested and analyzed using Western blotting, quantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry.
  
  
  RESULTS
  The HIF-2α mRNA and protein levels were significantly increased in the Tg mice when compared with control mice. Tg mice had significantly increased skin flap survival areas (72.0% ± 2.7%) when compared with wild-type mice (45.7% ± 1.1%). Moreover, histological examination revealed an increase in the subcutaneous blood vessel counts in the Tg mice.
  
  
  CONCLUSIONS
  Specific overexpression of HIF-2α in ECs promoted vascularization and enhanced skin flap survival in vivo in a mouse model.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Morimoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Imanishi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kihira
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa-Ishizawa
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Takaku
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hashimoto
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan; Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan; and Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki