Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival
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 ex...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2014-04-01
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| Series: | Plastic and Reconstructive Surgery, Global Open |
| Online Access: | http://journals.lww.com/prsgo/Fulltext/2014/04000/Article.10.aspx |
| _version_ | 1819020634648215552 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Atsushi Morimoto, MD |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T03:54:20Z |
| format | Article |
| id | doaj.art-ba7af31bebd7432cb1433fef779b13bf |
| institution | Directory Open Access Journal |
| issn | 2169-7574 |
| language | English |
| last_indexed | 2024-12-21T03:54:20Z |
| publishDate | 2014-04-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Plastic and Reconstructive Surgery, Global Open |
| spelling | doaj.art-ba7af31bebd7432cb1433fef779b13bf2022-12-21T19:16:53ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742014-04-0124e13210.1097/GOX.000000000000008301720096-201404000-00010Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap SurvivalAtsushi Morimoto, MD0Shuhei Tomita, MD, PhD1Masaki Imanishi, MS2Go Shioi, PhD3Yoshitaka Kihira, PhD4Yuki Izawa-Ishizawa, MD, PhD5Mitsuru Takaku, MD, PhD6Ichiro Hashimoto, MD, PhD7Yasumasa Ikeda, MD, PhD8Hideki Nakanishi, MD, PhD9Toshiaki Tamaki, MD, PhD10From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, JapanDivision of Molecular Pharmacology, Tottori University Faculty of Medicine, Nishi-cho, Yonago, JapanDepartment of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Chuou-ku, Kobe, Japan.Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, JapanFrom the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, JapanDepartment of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;From the Department of Plastic and Reconstructive Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, JapanDepartment of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan;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.http://journals.lww.com/prsgo/Fulltext/2014/04000/Article.10.aspx |
| spellingShingle | 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 Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival Plastic and Reconstructive Surgery, Global Open |
| title | Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival |
| title_full | Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival |
| title_fullStr | Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival |
| title_full_unstemmed | Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival |
| title_short | Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival |
| title_sort | overexpressed hif 2α in endothelial cells promotes vascularization and improves random pattern skin flap survival |
| url | http://journals.lww.com/prsgo/Fulltext/2014/04000/Article.10.aspx |
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