Beta 1 blockers improve survival and provide cardioprotection in septic mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31175 | GEO | 2015/08/03
SECONDARY ACCESSION(S): PRJNA144767
REPOSITORIES: GEO
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Project description:Septic cardiac dysfunction is a key feature of severe sepsis and septic shock, contributing to multiorgan dysfunction syndrome and death. It has been established that persistent beta adrenergic stimulation is detrimental in sepsis, and that specific beta 1 blockade mitigates excessive systemic inflammation and improves myocardial function. The aim of this study was to investigate the effects of specific beta 1 blocker esmolol on septic mouse myocardium by genomic and proteomic techniques. We also evaluated survival of septic mice and systemic inflammation under esmolol treatment. C57BL/6 mice were rendered septic by 2 models: cecal ligature and perforation (CLP) and intraperitoneal injection of lipopolysaccharides (LPS). Effects of esmolol on myocardium were assessed by microarray technique. Total RNA were isolated and purified from a 30mg sample of the heart of 6 groups of 8 animals, depending on the sepsis model and the treatment. The labeled cDNA from the treated animals were hybridized against the labeled cDNA from the untreated animals with 2 dye-swaps done for each sepsis model.
2015-08-03 | E-GEOD-31175 | biostudies-arrayexpress
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.
2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Keywords: Normal vs diseased
2008-12-12 | GSE13904 | GEO
Project description:Goal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients. Background: We measured gene expression levels and profiles of children with systemic inflammatory response syndrome (SIRS) and septic shock as a means for discovering patient sub-groups and gene signatures that are active in disease-affected individuals and potentially in patients with poor outcomes. Methods: Microarray and bioinformatics analyses of 123 microarray chips representing whole blood derived RNA from controls, children with SIRS, and children with septic shock. Results: A discovery-based filtering approach was undertaken to identify genes whose expression levels were altered in patients with SIRS or septic shock. Clustering of these genes identified 3 Major and several minor sub-groups of patients with SIRS or septic shock. The three groups differed with respect to incidence of septic shock and trended toward differences in mortality. Statistical analyses demonstrated that 6,435 gene probes were differentially regulated between the three patient sub-groups (false discovery rate < 0.001%). Of these gene probes, 623 gene probes within 7 major gene ontologies accounted for the majority of group differentiation. Network analyses of these 623 gene probes demonstrated 5 major gene networks that were differentially expressed between the 3 groups. Statistical comparison of septic shock survivors and non-survivors identified one major gene network that was under expressed in a high fraction of the non-survivors and identified potential biomarkers for poor outcome. Conclusions: This is the first genome-level demonstration of pediatric patient sub-groups with SIRS and septic shock. The sub-groups differ clinically and differentially express 5 major gene networks. We have identified gene signatures and potential biomarkers associated with poor outcome in children with septic shock. These data represent a major advancement in our genome-level understanding of pediatric SIRS and septic shock. Experiment Overall Design: Children < 10 years of age admitted to the pediatric intensive care unit and meeting the criteria for either SIRS or septic shock were eligible for the study. SIRS and septic shock were defined based on pediatric-specific criteria. We did not use separate categories of "sepsis" or "severe sepsis". Patients meeting criteria for "sepsis" or "severe sepsis" were placed in the categories of SIRS and septic shock, respectively, for study purposes. Control patients were recruited from the outpatient or inpatient departments of the participating institutions using the following exclusion criteria: a recent febrile illness (within 2 weeks), recent use of anti-inflammatory medications (within 2 weeks), or any history of chronic or acute disease associated with inflammation. Experiment Overall Design: After obtaining informed consent, blood samples were obtained on Day 1 of the study, and when possible on Day 3 of the study. Blood samples were divided for RNA extraction and isolation of serum. Severity of illness was calculated based on the PRISM III score. Organ failure was defined based on pediatric-specific criteria. Annotated clinical and laboratory data were collected daily while in the intensive care unit. Study patients were placed in the study categories of SIRS or Septic Shock on Day 1 of the study. On Day 3 of the study, patients were classified as SIRS, Septic Shock, or SIRS resolved (no longer meeting criteria for SIRS). All study patients were followed for 28 days to determine mortality or survival. Clinical, laboratory, and biological data were entered and stored using a web-based data base developed locally.
2008-06-13 | E-GEOD-4607 | biostudies-arrayexpress
Project description:Sepsis is defined as a systemic inflammatory response secondary to a proven or suspected infection. Mechanisms governing this inflammatory response have been shown to be complex and dynamic, involving cross-talking among diverse signaling pathways. However, current knowledge on mechanisms underlying sepsis is far from providing a complete picture of the syndrome, justifying additional efforts that might add to this scenario. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis: the analysis of gene transcription at the genome level potentially avoids results derived from biased assumptions. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor and non-survivor septic patients. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia. Global gene expression profiling allowed us to characterize early sepsis, as compared to healthy individuals. Our results corroborate literature reports on inflammation response in the early stages of sepsis but highlight great heterogeneity in gene expression during sepsis progress. Additionally, global gene expression in the early stage was also able to distinguish sepsis from septic shock and correlated with patient outcome. Differences in oxidative stress seem to be associated with clinical outcome, since significant differences in the expression profile of related genes were observed between survivors and non-survivors at the time of patient enrollment (early sepsis). However, our results substantiate current knowledge supporting that sepsis syndrome development is indeed multifaceted. Although the initial infection of enrolled patients was pneumonia, seven days later gene expression profiles seemed to be characteristic of each patient, common gene expression changes distinguishing survivors from non-survivors. This result could be associated with the underlying health status of each one of them, with complications due to sepsis itself as well as with distinct timing for response to treatment. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor (n=5) and non-survivor (n=5) septic patients, as well as from 3 healthy controls. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia.
2014-06-20 | E-GEOD-48080 | biostudies-arrayexpress
Project description:Clinically, cardiac dysfunction is a key component of sepsis-induced multi-organ failure. Mitochondrial function is essential for cardiomyocyte homeostasis as disrupted mitochondrial dynamics enhances mitophagy and apoptosis. However, therapies targeted to improve mitochondrial function in septic patients have not been explored. Our research is helpful to understand the role of cardiomyocyte PPARα in LPS-induced cardiac dysfunction
2023-04-20 | GSE229298 | GEO
Project description:Nowadays, there is no gold standard of sepsis diagnosis, thus there is a challenge to differentiate between shock septic and non-septic shock following a surgery, since patients with both conditions show similar signs and symptoms. In this sense, to get a quick and accurate diagnosis of septic shock is required to allow an immediate and specific treatment for this condition. In this work, we have evaluated the expression profile by microarray analysis from post-surgical septic shock and non-septic shock patients with the aim of proposing a candidate set genes as gold standard to help in distinguishing both conditions.
2020-08-16 | GSE131761 | GEO
Project description:Background: Sepsis can lead to multiple organ damage, and the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rate. However, the relative effect of disparate cell populations on sepsis induced myocardial dysfunction and the low-level tragus stimulation on it, remain unclear. Methods: We used the cardiac single-cell transcriptomic strategy to characterize the cardiac cell population and the network of cells that forms the heart. And we selected all cardiac macrophage from CD45+ cells using single-cell mRNA sequencing data. Then we used echocardiography performing, western blot and immunofluorescence and immunohistochemical technology to verify the data of the single-cell mRNA sequencing results. Results: In single-cell mRNA sequencing data, our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to sepsis induced myocardial dysfunction under low-level tragus stimulation. Pseudo timing analysis in single-cell sequencing showed that low level vagal nerve stimulation could induce the transformation of cardiac monocytes into M2 macrophages and play an anti-inflammatory role. After low-level tragus stimulation, the expression of α7nAChR in the heart tissue increased significantly. Echocardiography showed that low-level tragus stimulation could improve the cardiac function of septic myocardial injury of the mice. Comparing with the sepsis group, the expression of interleukin-1β in heart tissue of the mice in sepsis with low-level tragus stimulation group is significantly lower. Conclusion: Low-level tragus stimulation can improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages. Goal of the study: In the present study, we aimed to screen macrophages, their crosstalk with other cells, and macrophages associated with cardiac injury and further verify their origins and roles in the septic myocardial injury process and low-level tragus stimulation (LL-TS) to treat septic myocardial dysfunction.
2022-10-26 | GSE207363 | GEO
Project description:Sepsis induces systemic stress by augmenting inflammatory and pro-coagulant responses resulting in microvascular dysfunction and end organ failure, events modulated by the Protein C pathway. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene transcription yet their role in sepsis remains poorly defined. We hypothesized that aPC selectively alters the expression of specific miRNAs implicated in protection of hepatic function during septic shock. Male Sprague-Dawley rats underwent sham surgery or cecal ligation and puncture (CLP). Twenty-four later, animals were randomized and treated with aPC (1mg/kg) or vehicle (0.9% (w/v) saline) via an indwelling venous catheter at 12 hour intervals for 24 hours. Gene array was performed on hepatic RNA to determine miRNA expression, and predicted mRNA targets determined using a bioinformatics approach. Of 351 rat miRNAs examined by microarray hybridization, 17 were highly expressed during sepsis and restored to basal levels after aPC treatment. In silico analysis identified 9 miRNAs significantly regulating target genes of the focal adhesion pathway. These data suggest aPC treatment coordinates beneficial cytoprotective effects during sepsis by modulating miRNA expression. While translational effects remain to be fully elucidated in a clinical setting, we demonstrate herein the potential experimental and computational benefits for use of microRNA analysis in sepsis. 12 samples were analyzed. Microarray experiments were performed, in which liver tissue was harvested from variuous groups (Sham+Vehicle, Sham+aPC, CLP+Vehicle, CLP+aPC; n=3/group) and pooled.
2014-12-20 | E-GEOD-34790 | biostudies-arrayexpress
Project description:There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3677 genes, biological pathway analysis identified 86 genes significantly down-regulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis including lymphocyte depletion, reduced T lymphocyte activation and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of down-regulation found in non-survivors compared to survivors. The results show that whole blood gene-expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression based assay, to assess immunosuppression and guide immunotherapy in future clinical trials. Daily PAXgene samples for up to 5 days for sepsis survivors (n=26), sepsis nonsurvivors (n=9), and healthy controls (n=18).
2014-02-04 | E-GEOD-54514 | biostudies-arrayexpress