A longitudinal study highlights shared aspects of the transcriptomic response to cardiogenic and septic shock.
APACHE
Aged
Aged, 80 and over
Alarmins
/ analysis
Analysis of Variance
Belgium
DNA Replication
/ physiology
Female
Gene Expression Profiling
/ instrumentation
Humans
Inflammasomes
/ analysis
Intensive Care Units
/ organization & administration
Longitudinal Studies
Male
Middle Aged
Pilot Projects
Prospective Studies
Receptors, Interleukin
/ analysis
Receptors, Pattern Recognition
/ analysis
Sequence Analysis, RNA
/ methods
Shock, Cardiogenic
/ blood
Shock, Septic
/ blood
Switzerland
Cardiogenic shock
Circulatory shock
Critical illness
Immunoglobulin
PRR
RNA-Seq
Septic shock
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
19 12 2019
19 12 2019
Historique:
received:
25
05
2019
accepted:
12
11
2019
entrez:
21
12
2019
pubmed:
21
12
2019
medline:
2
6
2020
Statut:
epublish
Résumé
Septic 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. We 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. In 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. This 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. ClinicalTrials.gov, NCT02141607. Registered 19 May 2014.
Sections du résumé
BACKGROUND
Septic 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.
METHODS
We 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.
RESULTS
In 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.
CONCLUSIONS
This 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 REGISTRATION
ClinicalTrials.gov, NCT02141607. Registered 19 May 2014.
Identifiants
pubmed: 31856860
doi: 10.1186/s13054-019-2670-8
pii: 10.1186/s13054-019-2670-8
pmc: PMC6921511
doi:
Substances chimiques
Alarmins
0
Inflammasomes
0
Receptors, Interleukin
0
Receptors, Pattern Recognition
0
Banques de données
ClinicalTrials.gov
['NCT02141607']
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
414Subventions
Organisme : FP7 Health
ID : Grant agreement ID: 602706
Pays : International
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