Introduction The ex vivo lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation. Materials and methods Retrospective transcriptomics analyses were performed with peripheral tissue biopsies from “donation after brain death” lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP. Results 22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models. Conclusion EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation. Inflammation and cell death pathways are common molecular features of ischaemia–reperfusion and ischaemia–ex vivo lung perfusion. These may represent therapeutic targets for lung repair prior to transplantation. http://bit.ly/2sIrxOP

中文翻译：

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人类离体肺灌注期间肺修复的潜在治疗靶点

介绍 体外肺灌注 (EVLP) 技术已开发用于评估边缘供体肺的功能，并显着提高了供体肺的利用率。EVLP 也已被探索为通过抗生素或纤维蛋白溶解剂等损伤特异性治疗进行供体肺修复的平台。我们假设移植和 EVLP 之间共享的主动表达途径可能揭示了损伤的常见机制和移植前肺修复的潜在治疗靶点。材料和方法使用来自“脑死亡后捐赠”肺的外周组织活检进行回顾性转录组学分析，其中有 46 个移植前/移植后对和 49 个 EVLP 前/后对。通路分析用于识别和比较供体肺对移植和 EVLP 的反应。结果 22 条通路主要在移植中富集，包括淋巴细胞活化和细胞死亡的上调以及代谢的下调。EVLP 中主要富集了 8 条通路，包括白细胞功能的下调和血管过程的上调。27 条通路通常被丰富，包括先天性炎症的激活、细胞死亡、热应激以及代谢和蛋白质合成的下调。在炎症簇中，Toll 样受体/先天免疫信号转导接头信号的节点数量最多，并且是炎症的核心。这些机制以前被推测为动物模型中急性肺损伤的主要机制。结论 EVLP 和移植具有共同的损伤分子特征，包括先天性炎症和细胞死亡。在 EVLP 期间阻断这些通路可能允许在移植前进行肺修复。炎症和细胞死亡途径是缺血-再灌注和缺血-离体肺灌注的常见分子特征。这些可能代表移植前肺修复的治疗靶点。http://bit.ly/2sIrxOP