内皮细胞中过表达的缺氧诱导因子-2α促进血管生成并改善随意型皮瓣存活。
Overexpressed HIF-2α in Endothelial Cells Promotes Vascularization and Improves Random Pattern Skin Flap Survival.
作者信息
Morimoto Atsushi, Tomita Shuhei, Imanishi Masaki, Shioi Go, Kihira Yoshitaka, Izawa-Ishizawa Yuki, Takaku Mitsuru, Hashimoto Ichiro, Ikeda Yasumasa, Nakanishi Hideki, Tamaki Toshiaki
机构信息
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.
出版信息
Plast Reconstr Surg Glob Open. 2014 May 7;2(4):e132. doi: 10.1097/GOX.0000000000000083. eCollection 2014 Apr.
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.
背景
局部皮瓣手术在重建中非常有用。然而，循环衰竭导致的皮瓣坏死可能发生在其远端部分。内皮细胞（ECs）中的缺氧诱导因子（HIFs）有助于维持内皮细胞并促进血管生成，且HIF-2α在内皮细胞中大量表达。然而，HIF-2α在内皮细胞中的作用机制尚未完全阐明。本研究的目的是评估内皮细胞中HIF-2α过表达对皮瓣存活的体内影响。
方法
在具有内皮细胞特异性HIF-2α条件性过表达的转基因小鼠（Tg小鼠）和野生型同窝对照小鼠（n = 6）的背部掀起一个随机模式皮瓣（1.0×3.0 cm）。在术后第7天评估皮瓣存活情况。从皮瓣中采集组织样本，并使用蛋白质免疫印迹法、定量逆转录聚合酶链反应和免疫组织化学进行分析。
结果
与对照小鼠相比，Tg小鼠中HIF-2α的mRNA和蛋白质水平显著升高。与野生型小鼠（45.7%±1.1%）相比，Tg小鼠的皮瓣存活面积显著增加（72.0%±2.7%）。此外，组织学检查显示Tg小鼠皮下血管计数增加。
结论
在小鼠模型中，内皮细胞中HIF-2α的特异性过表达促进了血管生成并增强了皮瓣在体内的存活。
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