Factors affecting biomarkers of endothelial and alveolar epithelial dysfunction.
Factors affecting biomarkers of endothelial and alveolar epithelial dysfunction.
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影响内皮和肺泡上皮功能障碍生物标志物的因素。
DOI：
10.1007/s00134-016-4460-y
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发表时间：
2016
影响因子：
38.9
通讯作者：
Shime N
中科院分区：
文献类型：
--
作者：
Kyo M;Ohshimo S;Shime N
我们饶有兴趣地阅读了Yehya等人在最近一期《重症监护医学》上发表的文章[1]。他们前瞻性地研究了82例儿童急性呼吸窘迫综合征(PARDS)患者中血管生成素-2(Ang2)和晚期糖基化终产物可溶性受体(SRAGE)与死亡率的关系。结果显示，死亡者血浆Ang2和sRAGE水平高于存活者，且这些水平与非肺器官衰竭的数量相关。由于这些是评估PARDS患者内皮和肺泡上皮功能障碍的重要发现，我们非常感谢这项研究提供了临床有用的信息。然而，应该讨论几个可能影响当前结果的因素。首先，需要考虑SRAGE的生物动力学。在一项对405名危重患者和71名对照受试者的研究中，Ingels等人。结果显示，患者入院时的sRAGE水平显著高于对照组[2]。然而，到第7天，sRAGE水平下降到低于对照组的水平，并保持在较低水平[2]。这一发现可能部分反映了大量炎症的急性高峰期通过蛋白分解机制引起的受体脱落。在这项研究中，PARDS发病后24-48小时内的大范围采血时间可能影响了SRAGE水平的差异。其次，本研究中Ang2和SRAGE表达的发病机制有待进一步探讨。以往的研究表明，Ang2肽主要表达于血管内皮细胞[3]，而sRAGE主要表达于健康人肺泡I型上皮细胞和血管内皮细胞的基底膜[4]。然而，血管紧张素转换酶2和sRAGE在PARDS患者中的主要表达部位尚不清楚。这些标记物与本研究中观察到的非肺器官衰竭的数量之间的显著相关性表明，这些标记物在非肺器官中有显著的蛋白表达。在《纸牌》中，Ang2和Sage最强烈地代表的器官衰竭类型尚不清楚。对这些蛋白在肺和其他器官中表达的病理学研究将有助于更好地了解Ang2和sRAGE产生的主要部位。第三，应考虑伴随药物的影响。SRAGE的配体之一是高迁移率族蛋白1，它可以改变多种转录因子的活性，包括皮质类固醇受体和核因子-kappa B[5]。血管紧张素转换酶2与血管通透性有关，血管通透性可影响液体超载。有关可能影响炎症和感染的伴随治疗的信息，包括皮质类固醇、抗生素和液体平衡，将是有帮助的。
We read with interest the article by Yehya et al.[1] in a recent issue of Intensive Care Medicine. They prospectively studied the associations of angiopoietin-2 (Ang2) and soluble receptor of advanced glycation end products (sRAGE) with mortality in 82 patients with pediatric acute respiratory distress syndrome (PARDS). They showed that plasma Ang2 and sRAGE levels were higher in non-survivors than in survivors, and these levels were correlated with the number of non-pulmonary organ failures. Because these are important findings for evaluating endothelial and alveolar epithelial dysfunction in PARDS, we greatly appreciate this research for providing clinically useful information. However, several factors potentially affecting the current results should be discussed. First, the biokinetics of sRAGE need to be considered. In a study of 405 critically ill patients and 71 control subjects, Ingels et al. showed that sRAGE levels on admission were significantly higher in patients than in controls [2]. However, sRAGE levels decreased to levels lower than those in controls by day 7, and remained low [2]. This finding may partially reflect receptor shedding via a proteolytic mechanism induced by an acute peak of massive inflammation. The wide range of blood collection timing within 24–48 h of onset of PARDS in this study may have affected the variance in sRAGE levels. Second, the pathogenesis of Ang2 and sRAGE expression in this study needs to be discussed. Previous studies showed that Ang2 peptide was predominantly expressed in vascular endothelial cells [3] and sRAGE was expressed on the basal membrane of alveolar type I epithelial cells and vascular endothelial cells in healthy subjects [4]. However, primary sites of Ang2 and sRAGE expression in patients with PARDS are not well known. Significant correlations between these markers and the number of non-pulmonary organ failures observed in this study suggest significant protein expression of these markers in non-pulmonary organs. The type of organ failure that Ang2 and sRAGE most strongly represents in PARDS is unknown. A pathological investigation on expression of these proteins in the lungs and other organs would be helpful for better understanding of the primary sites of Ang2 and sRAGE production. Third, the effect of concomitant drugs should be considered. One of the ligands of sRAGE is high mobility group box protein 1, which modifies various activities of transcription factors, including corticosteroid receptors and nuclear factor-kappa B [5]. Ang2 is associated with vascular permeability, which can affect fluid overload. Information on concomitant therapies potentially affecting inflammation and infection, including corticosteroids, antibiotics, and fluid balance, would be helpful.