Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival

Atsushi Morimoto, MD; Shuhei Tomita, MD, PhD; Masaki Imanishi, MS; Go Shioi, PhD; Yoshitaka Kihira, PhD; Yuki Izawa-Ishizawa, MD, PhD; Mitsuru Takaku, MD, PhD; Ichiro Hashimoto, MD, PhD; Yasumasa Ikeda, MD, PhD; Hideki Nakanishi, MD, PhD; Toshiaki Tamaki, MD, PhD

doi:10.1097/GOX.0000000000000083

Plastic and Reconstructive Surgery, Global Open (Apr 2014)

Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival

Atsushi Morimoto, MD,
Shuhei Tomita, MD, PhD,
Masaki Imanishi, MS,
Go Shioi, PhD,
Yoshitaka Kihira, PhD,
Yuki Izawa-Ishizawa, MD, PhD,
Mitsuru Takaku, MD, PhD,
Ichiro Hashimoto, MD, PhD,
Yasumasa Ikeda, MD, PhD,
Hideki Nakanishi, MD, PhD,
Toshiaki Tamaki, MD, PhD

Affiliations

Atsushi Morimoto, MD: From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan
Shuhei Tomita, MD, PhD: Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, Japan
Masaki Imanishi, MS: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;
Go Shioi, PhD: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.
Yoshitaka Kihira, PhD: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;
Yuki Izawa-Ishizawa, MD, PhD: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;
Mitsuru Takaku, MD, PhD: From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan
Ichiro Hashimoto, MD, PhD: From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan
Yasumasa Ikeda, MD, PhD: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;
Hideki Nakanishi, MD, PhD: From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan
Toshiaki Tamaki, MD, PhD: Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;

DOI: https://doi.org/10.1097/GOX.0000000000000083
Journal volume & issue: Vol. 2, no. 4
p. e132

Abstract

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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.

Published in Plastic and Reconstructive Surgery, Global Open

ISSN: 2169-7574 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://www.prsgo.com

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