Henn Dominic, Abu-Halima Masood, Falkner Florian, Wermke Dominik, Meme Lilian G, Kühner Clemens, Keller Andreas, Kneser Ulrich, Meese Eckart, Schmidt Volker J
From the Department of Hand, Plastic, and Reconstructive Surgery, University of Heidelberg, BG Trauma Center Ludwigshafen; the Institute of Human Genetics and the Institute of Clinical Bioinformatics, Saarland University; and the Department of Vascular Surgery, Ludwigshafen Hospital.
Ludwigshafen, Homburg-Saar, and Saarbruecken, Germany.
Plast Reconstr Surg. 2018 Oct;142(4):489e-502e. doi: 10.1097/PRS.0000000000004750.
The placement of arteriovenous loops can enable microvascular anastomoses of free flaps when recipient vessels are scarce. In animal models, elevated fluid shear stress in arteriovenous loops promotes neoangiogenesis. Anecdotal reports in patients indicate that vein grafts used in free flap reconstructions of ischemic lower extremities are able to induce capillary formation. However, flow-stimulated angiogenesis has never been systematically investigated in humans, and it is unclear whether shear stress alters proangiogenic signaling pathways within the vascular wall of human arteriovenous loops.
Eight patients with lower extremity soft-tissue defects underwent two-stage reconstruction with arteriovenous loop placement, and free flap anastomoses to the loops 10 to 14 days later. Micro-RNA (miRNA) and gene expression profiles were determined in tissue samples harvested from vein grafts of arteriovenous loops by microarray analysis and quantitative real-time polymerase chain reaction. Samples from untreated veins served as controls.
A strong deregulation of miRNA and gene expression was detected in arteriovenous loops, showing an overexpression of angiopoietic cytokines, oxygenation-associated genes, vascular growth factors, and connexin-43. The authors discovered inverse correlations along with validated and bioinformatically predicted interactions between angiogenesis-regulating genes and miRNAs in arteriovenous loops.
The authors' findings demonstrate that elevated shear stress triggers proangiogenic signaling pathways in human venous tissue, indicating that arteriovenous loops may have the ability to induce neoangiogenesis in humans. The authors' data corroborate the nutrient flap hypothesis and provide a molecular background for arteriovenous loop-based tissue engineering with potential clinical applications for soft-tissue defect reconstruction.
当受区血管稀缺时，动静脉袢的植入可实现游离皮瓣的微血管吻合。在动物模型中，动静脉袢中升高的流体剪切应力可促进新生血管形成。患者的轶事报道表明，用于缺血性下肢游离皮瓣重建的静脉移植物能够诱导毛细血管形成。然而，血流刺激的血管生成在人类中从未得到系统研究，目前尚不清楚剪切应力是否会改变人类动静脉袢血管壁内的促血管生成信号通路。
8例下肢软组织缺损患者接受了两阶段重建，先植入动静脉袢，10至14天后将游离皮瓣与动静脉袢进行吻合。通过微阵列分析和定量实时聚合酶链反应，测定从动静脉袢静脉移植物采集的组织样本中的微小RNA（miRNA）和基因表达谱。未处理静脉的样本用作对照。
在动静脉袢中检测到miRNA和基因表达的强烈失调，显示血管生成细胞因子、氧合相关基因、血管生长因子和连接蛋白-43的过表达。作者发现了动静脉袢中血管生成调节基因与miRNA之间的反向相关性以及经过验证和生物信息学预测的相互作用。
作者的研究结果表明，升高的剪切应力触发了人类静脉组织中的促血管生成信号通路，表明动静脉袢可能具有在人类中诱导新生血管形成的能力。作者的数据证实了营养皮瓣假说，并为基于动静脉袢的组织工程提供了分子背景，具有软组织缺损重建的潜在临床应用价值。
