Abstract
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.
Highlights
Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology
Twenty-one septic shock and 11 cardiogenic shock patients (Additional file 1) were eligible for the present study, after excluding 16 patients who did not meet the inclusion criteria and 31 patients who did not have blood samples collected at the three time points (Additional file 2)
Laboratory results from the blood collected at the three time points of interest, revealed significant differences between cardiogenic and septic shock patients for C-reactive protein (CRP) level, lymphocyte count, hematocrit, and fibrinogen (p < 0.05) (Table 1)
Summary
Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. CS, on the other hand, results from acutely depressed cardiac output secondary to cardiac pump failure, with myocardial infarction as its most common cause and systemic inflammation evolving later in response Both types of circulatory shock are associated with high mortality: 30% for SS [5] and 40% in CS [6]. We performed a longitudinal study with a time course RNA sequencing analysis in order to explore the transcriptome in the whole blood of septic and cardiogenic shock patients during the first 7 days of ICU stay. The purpose of this pilot analysis was to highlight the transcriptomic signatures common to CS and SS, using septic patients without shock as controls
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