Proteomic profiles in acute respiratory distress syndrome differentiates survivors from non-survivors.

Proteomic profiles in acute respiratory distress syndrome differentiates survivors from non-survivors.
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DOI:
10.1371/journal.pone.0109713
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wendt CH
Wendt CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bhargava M;Becker TL;Viken KJ;Jagtap PD;Dey S;Steinbach MS;Wu B;Kumar V;Bitterman PB;Ingbar DH;Wendt CH

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急性呼吸窘迫综合征(ARDS)的死亡率仍然很高。目前,还没有生物标志物提供可靠的预后信息来指导临床管理或对临床试验参与者进行风险分层。本研究的目的是探测支气管肺泡灌洗液(BALF)蛋白质组,以识别区分ARDS幸存者和非幸存者的蛋白质。根据ARDS机械通气开始时间(第1天)将患者分为早期(1 ~ 7天)和晚期(8 ~ 35天)组。采用LC MS/MS对来自早期幸存者(n = 7)、早期非幸存者(n = 8)和晚期幸存者(n = 7)的中丰度和低丰度蛋白质富集的BALF进行绝对和相对定量等压标记(iTRAQ)。在全球错误发现率为1%的724种蛋白质中,有499种可以获得定量信息。在早期ARDS中,幸存者体内丰富的蛋白质与机体相关,表明机体对损伤和应激有协调的代偿反应。包括凝血和纤溶;免疫系统激活;阳离子和铁的体内平衡。在早期非幸存者中,蛋白质更丰富,参与碳水化合物分解代谢和胶原合成,没有激活代偿反应。在早期幸存者中观察到的代偿性免疫激活和离子稳态反应在晚期幸存者中转变为细胞迁移和基于肌动蛋白丝的过程,揭示了随着肺愈合,BALF蛋白质组的动态变化。区分幸存者和非幸存者的早期蛋白是预测ARDS患者生存的候选生物标志物。
Acute Respiratory Distress Syndrome (ARDS) continues to have a high mortality. Currently, there are no biomarkers that provide reliable prognostic information to guide clinical management or stratify risk among clinical trial participants. The objective of this study was to probe the bronchoalveolar lavage fluid (BALF) proteome to identify proteins that differentiate survivors from non-survivors of ARDS. Patients were divided into early-phase (1 to 7 days) and late-phase (8 to 35 days) groups based on time after initiation of mechanical ventilation for ARDS (Day 1). Isobaric tags for absolute and relative quantitation (iTRAQ) with LC MS/MS was performed on pooled BALF enriched for medium and low abundance proteins from early-phase survivors (n = 7), early-phase non-survivors (n = 8), and late-phase survivors (n = 7). Of the 724 proteins identified at a global false discovery rate of 1%, quantitative information was available for 499. In early-phase ARDS, proteins more abundant in survivors mapped to ontologies indicating a coordinated compensatory response to injury and stress. These included coagulation and fibrinolysis; immune system activation; and cation and iron homeostasis. Proteins more abundant in early-phase non-survivors participate in carbohydrate catabolism and collagen synthesis, with no activation of compensatory responses. The compensatory immune activation and ion homeostatic response seen in early-phase survivors transitioned to cell migration and actin filament based processes in late-phase survivors, revealing dynamic changes in the BALF proteome as the lung heals. Early phase proteins differentiating survivors from non-survivors are candidate biomarkers for predicting survival in ARDS.
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发表时间: 1997-01-01
影响因子: 24.7
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发表时间: 2013-07
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