BackgroundSeptic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock.MethodsWe performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value < 0.01 (Benjamini-Hochberg multiple test correction) were defined differentially expressed (DEGs). We used gene set enrichment analysis (GSEA) to identify the biological processes and transcriptional regulators significantly enriched in both types of shock.ResultsIn both CS and SS patients, GO terms of inflammatory response and pattern recognition receptors (PRRs) were downregulated following ICU admission, whereas gene sets of DNA replication were upregulated. At the gene level, we observed that alarmins, interleukin receptors, PRRs, inflammasome, and DNA replication genes significantly changed their expression in CS and SS, but not in SC. Analysis of transcription factor targets showed in both CS and SS patients, an enrichment of CCAAT-enhancer-binding protein beta (CEBPB) targets in genes downregulated over time and an enrichment of E2F targets in genes with an increasing expression trend.ConclusionsThis pilot study supports, within the limits of a small sample size, the role of alarmins, PRRs, DNA replication, and immunoglobulins in the pathophysiology of circulatory shock, either in the presence of infection or not. We hypothesize that these genes could be potential targets of therapeutic interventions in CS and SS.Trial registrationClinicalTrials.gov, NCT02141607. Registered 19 May 2014.

中文翻译：

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一项纵向研究强调了对心源性和感染性休克的转录组反应的共同方面

背景感染性休克 (SS) 和心源性休克 (CS) 是两种病因不同的循环性休克。几项研究描述了 SS 患者的分子改变，而对 CS 中涉及的分子因素的研究却很少。我们旨在评估 CS 和 SS 患者的全血中，使用未休克 (SC) 的脓毒症患者作为对照，在入住 ICU 后超过 1 周内发生的转录组修饰是两种类型的休克常见的。方法我们进行了全血 RNA在 21 SS、11 CS 和 5 SC 中进行测序。对于休克患者，在入住 ICU 后 16 小时内（T1）、入住 ICU 后 48 小时（T2）和第 7 天或出院前（T3）采集血样。在对照中，血液样本在 T1 和 T2 可用。已经在 CS、SS、和 SC 分别进行配对分析。p 值 < 0.01（Benjamini-Hochberg 多重检验校正）的基因被定义为差异表达（DEG）。我们使用基因集富集分析 (GSEA) 来确定两种类型休克中显着富集的生物学过程和转录调节因子。 结果在 CS 和 SS 患者中，炎症反应和模式识别受体 (PRR) 的 GO 术语在入住 ICU 后下调，而 DNA 复制的基因组被上调。在基因水平上，我们观察到警报素、白细胞介素受体、PRR、炎症小体和 DNA 复制基因显着改变了它们在 CS 和 SS 中的表达，但在 SC 中没有。在 CS 和 SS 患者中显示的转录因子靶标分析，随着时间的推移，基因中 CCAAT 增强子结合蛋白 β (CEBPB) 靶标的富集以及表达趋势增加的基因中 E2F 靶标的富集。循环休克病理生理学中的警报素、PRR、DNA 复制和免疫球蛋白，无论是否存在感染。我们假设这些基因可能是 CS 和 SS 治疗干预的潜在靶标。Trial registrationClinicalTrials.gov, NCT02141607。2014 年 5 月 19 日注册。循环休克病理生理学中的免疫球蛋白，无论是否存在感染。我们假设这些基因可能是 CS 和 SS 治疗干预的潜在靶标。Trial registrationClinicalTrials.gov, NCT02141607。2014 年 5 月 19 日注册。循环休克病理生理学中的免疫球蛋白，无论是否存在感染。我们假设这些基因可能是 CS 和 SS 治疗干预的潜在靶标。Trial registrationClinicalTrials.gov, NCT02141607。2014 年 5 月 19 日注册。