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呼出气体冷凝物中急性肺栓塞的潜在生物标志物。

Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate.

作者信息

Gade Inger Lise, Schultz Jacob Gammelgaard, Brøndum Rasmus Froberg, Kjærgaard Benedict, Nielsen-Kudsk Jens Erik, Andersen Asger, Kristensen Søren Risom, Honoré Bent

机构信息

Department of Hematology and Clinical Cancer Research Center, Aalborg University Hospital, 9000 Aalborg, Denmark.

Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark.

出版信息

J Clin Med. 2021 Nov 4;10(21):5165. doi: 10.3390/jcm10215165.

Abstract

Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography-tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, -value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE.

摘要

目前用于肺栓塞(PE)的诊断标志物缺乏特异性。我们在急性PE猪模型中研究了呼出气冷凝液(EBC)的蛋白质组,以确定PE的潜在诊断标志物。在14头猪诱导自体中度风险PE后及基线时收集EBC,另外还有4头阴性对照猪。使用无标记定量纳米液相色谱-串联质谱分析EBC的蛋白质谱。在猪的EBC中总共鉴定出897种蛋白质。与基线和阴性对照相比,PE后145种不同蛋白质的水平发生了变化:白蛋白是上调最明显的蛋白质之一,PE后2.5小时其水平高出14倍(P值:0.02)。PE后其他49种蛋白质的水平高出1.3至17.1倍。PE后95种蛋白质的水平降低。中性粒细胞明胶酶相关脂质运载蛋白(倍数变化0.3,P值<0.01)是PE后2.5小时减少最明显的蛋白质之一。基于惩罚回归的预测模型鉴定出包括白蛋白和中性粒细胞明胶酶相关脂质运载蛋白在内的5种蛋白质。该模型能够在27个样本中的22个样本中正确区分基线样本和PE后2.5小时收集的EBC样本。总之,急性PE猪模型中的EBC含有几种PE的潜在诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9295/8584843/03eb67ef4cb8/jcm-10-05165-g001.jpg

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