Chronic sleep fragmentation reduces left ventricular contractile function and alters gene expression related to innate immune response and circadian rhythm in the mouse heart
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PROVIDER: PRJNA990695 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The purpose of this study was to comprehensively identify the gene expression changes that occur after chronic sleep fragmentation. Method: We conducted total microarray analysis of the heart in mice following 5 weeks of sleep fragmentation. Results: The microarray analysis revealed significant and dramatic gene expression changes in the mouse heart as a result of chronic sleep fragmentation. Conclusion: This study provides valuable insights into the biological impact of chronic sleep fragmentation, shedding light on the molecular mechanisms involved.
2024-07-31 | GSE236358 | GEO
Project description:It remains unclear how sleep influences inflammatory pathways after myocardial infarction (SF). In this study, we relied on established murine models and assessed how sleep fragmentation (SF) alters transcriptional programing in the blood, heart, and brain after MI.
2024-10-30 | GSE275089 | GEO
Project description:Background: Late gestational sleep fragmentation (LG-SF) is one of the major perturbations associated with sleep apnea and other sleep disorders during pregnancy. Objectives: To investigate the effects of late LG-SF on the epigenome of visceral white adipose tissue (VWAT) in the offspring. Methods: Time-pregnant mice were exposed to LG-SF or control sleep (LG-SC) conditions during the last 6 days of gestation. We performed large-scale DNA methylation analyses using MeDIP coupled to microarrays (MeDIP-chip) in VWAT of 24-week-old LG-SF and LG-SC offspring (n=8 mice/group). Univariate multiple-testing adjusted statistical analyses were applied to identify differentially methylated regions (DMRs) between the groups. DMRs were mapped to their corresponding genes, and tested for potential overlaps with biological pathways and gene networks. Results: We detected 2148 DMRs between LG-SF and LG-SC groups (p< 0.0001, MAT algorithm). A large proportion of the DMR-associated genes have reported functions that are altered in obesity and metabolic syndrome. Overrepresented pathways and gene networks were related to metabolic regulation and inflammatory response. Conclusions: Our findings show a major role for epigenomic regulation of pathways associated to metabolic processes and inflammatory response in VWAT. Furthermore, LG-SF-induced epigenetic alterations appear to increase the susceptibility to obesity and metabolic syndrome in the offspring. 16 mouse VWAT samples were analyzed by MeDIP coupled to microarray analysis: Offspring of mothers exposed to late-gestational sleep fragmentation (n=8, LG-SF group) and offspring of mothers mouse exposed to normal sleep conditions (n=8, LG-SC group)
2015-04-02 | E-GEOD-63208 | biostudies-arrayexpress
Project description:22 healthy volunteers without sleep disorders were resident in an environmental scheduling facility and participated in a forced-desynchrony protocol, in which the sleep-wake cycle and the associated fasting-feeding cycle is scheduled to a 28-hour period, of which one third (i.e. 9h 20min) is scheduled for sleep. Under these conditions, during which light levels in the waking episode are kept low and sleep is scheduled in darkness, the phase of the melatonin rhythm occurred at approximately the same clock time during the first (D1) and fourth (D4) 28-h cycle and there were no major changes in either the amplitude or the waveform of this rhythm. During D1 and D4 7 blood samples were taken, RNA was extracted from leukocytes, labelled and hybridised to human whole-genome microarrays A total of 287 samples comprising 22 human subjects, for which 14 samples across multiple time-points/sleep condition were collected.
2014-01-23 | E-GEOD-48113 | biostudies-arrayexpress
Project description:Background: Sustained sleep insufficiency impairs immune system and increases the adverse outcomes of cardiovascular diseases. However, the role and mechanisms prolonged sleep fragmentation (SF) on the outcomes of myocardial infarction (MI) remains elusive. Methods: Among 497 MI patients with complete sleep data participating in the National Health and Nutrition Examination Survey, the association between different types of sleep disorders and post-MI survivability was evaluated. We then developed a mouse model with 10 weeks of SF followed by MI surgery. Emergency hematopoiesis and neutrophil expansion were analyzed. Potential mechanisms were explored using bone marrow (BM) transplantation, anti-SiglecF neutralizing antibodies and Interferon alpha and beta receptor subunit 1 knockout (Ifnar1-/-) in BM. Results: Frequent nocturnal awakening independently predicted reduced survival rate of MI patients, with a hazard ratio (HR) of 2.136 (95% CI=1.142-3.995). Increased infarct size, deteriorated cardiac function and lower survival rate were also observed in MI mice pretreated with 10-week SF. SF facilitated post-MI neutrophil expansion and infiltration into infarct area, differentiating into SiglecFhi subset. Inhibition of SiglecFhi neutrophils allowed for the alleviations of post-MI cardiac remodeling. Furthermore, BM progenitors were skewed toward neutrophil lineage concomitant with the clonal expansion of granulocyte-monocyte progenitors (GMPs) in MI mice pretreated with 10-week SF. Transcriptome analysis and functional experiments revealed that activation of type I interferon (IFN) signaling was involved in this process, while depletion of Ifnar1 in BM and administration of IFNAR1-neutralizing antibodies significantly alleviated post-MI cardiac remodeling and neutrophil expansion. Conclusions: SF aggravates post-MI cardiac remodeling and dysfunction through promoting GMP differentiation and neutrophil expansion. Blockage of type I IFN could alleviate this detrimental influence.
2024-09-07 | GSE276317 | GEO
Project description:Background: Late gestational sleep fragmentation (LG-SF) is one of the major perturbations associated with sleep apnea and other sleep disorders during pregnancy. Objectives: To investigate the effects of late LG-SF on the epigenome of visceral white adipose tissue (VWAT) in the offspring. Methods: Time-pregnant mice were exposed to LG-SF or control sleep (LG-SC) conditions during the last 6 days of gestation. We performed large-scale DNA methylation analyses using MeDIP coupled to microarrays (MeDIP-chip) in VWAT of 24-week-old LG-SF and LG-SC offspring (n=8 mice/group). Univariate multiple-testing adjusted statistical analyses were applied to identify differentially methylated regions (DMRs) between the groups. DMRs were mapped to their corresponding genes, and tested for potential overlaps with biological pathways and gene networks. Results: We detected 2148 DMRs between LG-SF and LG-SC groups (p< 0.0001, MAT algorithm). A large proportion of the DMR-associated genes have reported functions that are altered in obesity and metabolic syndrome. Overrepresented pathways and gene networks were related to metabolic regulation and inflammatory response. Conclusions: Our findings show a major role for epigenomic regulation of pathways associated to metabolic processes and inflammatory response in VWAT. Furthermore, LG-SF-induced epigenetic alterations appear to increase the susceptibility to obesity and metabolic syndrome in the offspring.
2015-04-02 | GSE63208 | GEO
Project description:Note this data set has identical data files: Files GSM40994.txt and GSM40995.txt. GSE2240 contains two different experimental subsets:; 1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium); The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions (Barth AS et al., Eur J Physiol, 2005). 2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm. Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005).
2007-10-27 | E-GEOD-2240 | biostudies-arrayexpress
Project description:22 healthy volunteers without sleep disorders were resident in an environmental scheduling facility and participated in a forced-desynchrony protocol, in which the sleep-wake cycle and the associated fasting-feeding cycle is scheduled to a 28-hour period, of which one third (i.e. 9h 20min) is scheduled for sleep. Under these conditions, during which light levels in the waking episode are kept low and sleep is scheduled in darkness, the phase of the melatonin rhythm occurred at approximately the same clock time during the first (D1) and fourth (D4) 28-h cycle and there were no major changes in either the amplitude or the waveform of this rhythm. During D1 and D4 7 blood samples were taken, RNA was extracted from leukocytes, labelled and hybridised to human whole-genome microarrays
2014-01-23 | GSE48113 | GEO
Project description:4 healthy volunteers without sleep disorders were resident in an environmental scheduling facility and participated in a forced-desynchrony protocol, in which the sleep-wake cycle and the associated fasting-feeding cycle is scheduled to a 28-hour period, of which one third (i.e. 9h 20min) is scheduled for sleep. Under these conditions, during which light levels in the waking episode are kept low and sleep is scheduled in darkness, the phase of the melatonin rhythm occurred at approximately the same clock time during the first (D1) and fourth (D4) 28-h cycle and there were no major changes in either the amplitude or the waveform of this rhythm. During D1 and D4 7 blood samples were taken, RNA was extracted from leukocytes, labelled and hybridised to human whole-genome microarrays
2017-02-08 | GSE82113 | GEO
Project description:Myelination depends on maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knock out of Bmal1 in OPCs during development disrupts expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatio-temporal manner. Furthermore, these deficits translate into thinner myelin, dysregulated cognitive and motor function, and increased sleep fragmentation. OPC-specificBmal1loss in adulthood does not alter OPC density at baseline but impairs remyelination of a demyelinated lesion driven by changes in OPC morphology and migration. Lastly, we show sleep fragmentation is associated with increased prevalence of the demyelinating disorder multiple sclerosis (MS), suggesting a link between MS and sleep that requires further investigation. These findings have broad mechanistic and therapeutic implications for brain disorders that include both myelin and sleep phenotypes.
2023-09-07 | GSE239541 | GEO