Effect of landiolol on sex-related transcriptomic changes in myocardium during sepsis
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PROVIDER: PRJNA515045 | ENA |
REPOSITORIES: ENA
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Project description:We compared the myocardial transcriptional profiles in male and female rats after CLP (Cecal ligation and puncture) induction and landiolol administration. This analysis showed major differences between males and females in the biological processes activated during sepsis. In particular, a very significant decrease in processes related to cell organization, contractile function, ionic transport and PI3K-Akt signaling were observed only in males. Regarding the direct regulation of gene expression of the adrenergic pathway, there was no major differences between male and female. Moreover, our results highlighted the large number of signaling pathways dysregulated during sepsis in males that were reversed by landiolol. In particular, the level of expression of the genes encoding the contractile proteins, TUBA8 and MYH7B, the phosphatase PPP2CA, GRK5 and AKAP6 were close to their basal levels in males. In contrast, in females, only few pathways were affected by the action of landiolol. In addition, adrenergic signaling was decreased while genes potentially involved in calcium overload were overexpressed.
2019-01-15 | GSE125042 | GEO
Project description:ObjectivesThe aims of this study are to better understand phenotypic differences between male and female rats during sepsis, to characterise the contribution of the beta1-adrenergic blocker landiolol to septic cardiomyopathy and to determine why landiolol induces divergent effects in males and females.MethodsThe myocardial transcriptional profiles in male and female Wistar rats were assessed after the induction of sepsis by cecal ligation and puncture and addition of landiolol.ResultsOur results showed major differences in the biological processes activated during sepsis in male and female rats. In particular, a significant decrease in processes related to cell organisation, contractile function, ionic transport and phosphoinositide-3-kinase/AKT (PI3K/AKT) signalling was observed only in males. The transcript of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 (SERCA3) was sex-differently regulated. In males, landiolol reversed several signalling pathways dysregulated during sepsis. The expression level of genes encoding tubulin alpha 8 (TUBA8) and myosin heavy chain 7B (MYH7) contractile proteins, phosphatase 2 catalytic subunit alpha (PPP2CA), G protein-coupled receptor kinase 5 (GRK5) and A-kinase anchoring protein 6 (AKAP6) returned to their basal levels. In contrast, in females, landiolol had limited effects.ConclusionIn males, landiolol reversed the expression of many genes that were deregulated in sepsis. Conversely, sepsis-induced deregulation of gene expression was less pronounced in females than in males, and was maintained in the landiolol-treated females. These findings highlight important sex-related differences and confirm previous observations on the important benefit of landiolol intake on cardiac function in male rats.
| S-EPMC6701793 | biostudies-literature
Project description:Although in-hospital mortality rates for sepsis have decreased, survivors often experience lasting physical and cognitive deficits. Moreover, older adults are more vulnerable to long-term complications associated with sepsis. We employed a murine model to examine the influence of age and sex on the brain’s response and recovery following sepsis. Young (~4 months) and old (~20 months) mice (C57BL/6) of both sexes underwent cecal ligation and puncture (CLP) with restraint stress. The hippocampal transcriptome was examined in age and sex-matched controls at 1 and 4 days post-CLP. In general, immune and stress-related genes increased while neuronal, synaptic, and glial genes decreased one day after CLP-induced sepsis. However, specific age and sex differences were observed for the initial responsiveness to sepsis as well as the rate of recovery examined on day 4. Young females exhibited a muted transcriptional response relative to young males and old females. Old females exhibited a robust shift in gene transcription on day 1 and, while most genes recovered, genes linked to neurogenesis and myelination continued to be downregulated by day 4. In contrast, old males exhibited a more delayed or prolonged response to sepsis, such that neuronal and synaptic genes continued to decrease while immune response genes continued to increase on day 4. These results suggest that aging is associated with delayed recovery from sepsis, which is particularly evident in males.
2019-07-22 | GSE128925 | GEO
Project description:Sepsis related ACLF mouse model
| PRJNA950440 | ENA
Project description:Sepsis, defined as a life-threatening organ dysfunction caused by a dysregulated host immune response to infection, is a common and dangerous clinical syndrome. Sepsis results in an excessive host inflammatory response that can induce immediate and persistent cognitive decline, and this is known to be worse in older individuals. Sex-specific differences in the outcome of infectious diseases and sepsis appear to favor females. These differences likely involve sex steroids, sex chromosomes, and possibly epigenetic mechanisms. We employed a murine model to examine the influence of age and sex on the brain's microRNA (miR) response following sepsis. Young (~ 4 months) and old (~ 20 months) adult mice (C57BL/6) of both sexes underwent cecal ligation and puncture (CLP) with daily restraint stress. Differential expression of hippocampal miR was examined in age- and sex-matched controls at 1 and 4 days post-CLP. A sexually dimorphic miR response was observed. Similar to previous work examining the transcription profile, young females exhibited a better recovery of the miR profile from day1 to day4, relative to young males and old females. For young males and all female groups, the initial response mainly involved a decrease in miR expression. In contrast, old males exhibited only upregulated miR on day1 and day4, with 22 miR upregulated across days. Examination of the relationship of these 22 upregulated miR with mRNA expression indicated downregulation of mRNA with time from induction of sepsis and was more pronounced for mRNA that were associated with multiple upregulated miR. The results emphasize age and sex differences in epigenetic mechanisms that likely contribute sexually dimorphic responses to sepsis.
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Project description:Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission Goal of the study was to determine whether biologically relevant genes were identified to be differentially expressed genes in patients with sepsis alone and sepsis with ARDS Prospective observational study, case cohort design
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Project description:Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The global burden of sepsis is difficult to ascertain, although a recent scientific publication estimated that there were 48.9 million cases and 11 million sepsis-related deaths worldwide, which accounted for almost 20% of all global deaths. Here we analyzed the whole blood transcriptome of 5 healthy controls and 5 patients with confirmed sepsis from the Department of Emergency, Division of Surgical critical care, Tongji Trauma Center, Tongji Hospital, Tongji Medical College. This research aims to understand the expression of immune cells in sepsis patients and to construct an immune cell landscape of sepsis.
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Project description:Sex-related differences in Alzheimer’s disease
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Project description:AMPK related of circRNA expression in C57 male mice myocardium
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