机械转导诱导的皮肤新生血管的形态计量学研究。
A morphometric study of mechanotransductively induced dermal neovascularization.
机构信息
Boston, Mass.; Lausanne, Switzerland; and Mainz, Germany From the Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, and the Laboratory of Adaptive and Regenerative Biology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School; the Department of Plastic, Reconstructive, and Aesthetic Surgery, University Hospital of Lausanne; the Department of Surgery, Vascular Biology Program, Harvard Medical School, Children's Hospital Boston; and the Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz.
出版信息
Plast Reconstr Surg. 2011 Oct;128(4):288e-299e. doi: 10.1097/PRS.0b013e3182268b19.
BACKGROUND
Mechanical stretch has been shown to induce vascular remodeling and increase vessel density, but the pathophysiologic mechanisms and the morphologic changes induced by tensile forces to dermal vessels are poorly understood.
METHODS
A custom computer-controlled stretch device was designed and applied to the backs of C57BL/6 mice (n=38). Dermal and vascular remodeling was studied over a 7-day period. Corrosion casting and three-dimensional scanning electron microscopy and CD31 staining were performed to analyze microvessel morphology. Hypoxia was assessed by immunohistochemistry. Western blot analysis of vascular endothelial growth factor (VEGF) and mRNA expression of VEGF receptors was performed.
RESULTS
Skin stretching was associated with increased angiogenesis as demonstrated by CD31 staining and vessel corrosion casting where intervascular distance and vessel diameter were decreased (p<0.01). Immediately after stretching, VEGF dimers were increased. Messenger RNA expression of VEGF receptor 1, VEGF receptor 2, neuropilin 1, and neuropilin 2 was increased starting as early as 2 hours after stretching. Highly proliferating epidermal cells induced epidermal hypoxia starting at day 3 (p<0.01).
CONCLUSIONS
Identification of significant hypoxic cells occurred after identification of neovessels, suggesting an alternative mechanism. Increased expression of angiogenic receptors and stabilization of VEGF dimers may be involved in a mechanotransductive, prehypoxic induction of neovascularization.
背景
机械拉伸已被证明可诱导血管重塑和增加血管密度，但张力对真皮血管的病理生理机制和形态变化知之甚少。
方法
设计了一种定制的计算机控制拉伸装置，并将其应用于 C57BL/6 小鼠的背部（n=38）。在 7 天的时间内研究了真皮和血管重塑。进行了微血管形态学分析的腐蚀铸造和三维扫描电子显微镜以及 CD31 染色。通过免疫组织化学评估缺氧。进行了血管内皮生长因子（VEGF）的 Western blot 分析和 VEGF 受体的 mRNA 表达分析。
结果
皮肤拉伸与血管生成增加相关，这表现在 CD31 染色和血管腐蚀铸造中，血管间距离和血管直径减小（p<0.01）。拉伸后立即增加了 VEGF 二聚体。VEGF 受体 1、VEGF 受体 2、神经纤毛蛋白 1 和神经纤毛蛋白 2 的信使 RNA 表达从拉伸后 2 小时开始增加。高度增殖的表皮细胞在第 3 天开始引起表皮缺氧（p<0.01）。
结论
在识别出新血管后发现了大量缺氧细胞，这表明存在另一种机制。血管生成受体的表达增加和 VEGF 二聚体的稳定可能参与了机械转导、预缺氧诱导的新生血管形成。
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