Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA295993 | ENA |
REPOSITORIES: ENA
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Project description:Background: Obstructive sleep apnea (OSA) is a highly prevalent condition that is associated with a wide range of long-term morbidities including metabolic, cardiovascular, and cognitive alterations, possibly via activation of systemic inflammatory and oxidative stress pathways. Implementation of positive airway pressure (PAP) is the first line treatment for OSA. However, the molecular and cellular mechanisms underlying OSA-induced morbidities and their response to PAP treatment remain unclear. Methods And Results: DNA methylation profiles were examined in blood monocytes of OSA patients before and after PAP treatment. We identified 1,847 regions showing significant differential DNA methylation (p<0.001 and MAT score >4) between the groups. Analysis of biochemical pathways and gene networks demonstrated that differentially methylated regions (DMRs) were associated with immune responses, and particularly with mechanisms governing gene regulation by peroxisome proliferation-activated receptors (PPAR). Single locus quantitative PCR analysis revealed that DNA methylation was increased at the PPAR responsive elements (PPAREs) of 8 genes in the post-treatment samples, suggesting that PAP treatment leads to an increase in DNA methylation at PPAREs, possibly affecting the binding of the PPARG complex and downstream gene expression. Conclusions: Our work provides initial evidence of epigenetic regulation particularly involving metabolic pathways in OSA patients that are responsive to PAP treatment. We postulate that differentially methylated regions in blood monocytes may serve as potential biomarkers in clinical practice.
2016-05-11 | GSE73053 | GEO
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index ≥ 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures. Total RNA from peripheral blood leukocytes of 18 subjects with severe sleep apnea at baseline and after effective CPAP therapy was hybridized to 36 Affymetrix Genechip Human Gene 1.0 ST microarrays
2013-12-31 | E-GEOD-49800 | biostudies-arrayexpress
Project description:Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular morbidity and mortality. Epidemiological and animal models studies generate hypotheses for innovative strategies in OSA management by interfering intermediates mechanisms associated with cardiovascular complications. In this study, we interrogated DNA methylation profiles in 16 polysomnographically evaluated OSA patients (Apnea Hypopnea Index, AHI > 30) and 8 controls (AHI<5 events/h sleep). Blood samples were collected at initial visit (V1) and a year later (V2). OSA patients received Continuous Positive Air Pressure (CPAP) therapy with high adherence (> 4 hours/night). Control individuals did not receive CPAP therapy. Genomic DNA was treated with sodium bisulfite. Converted DNA was analyzed using Illumina’s Infinium Human Methylation 450 BeadChip assay. DNA methylation profiles enabled the prospective evaluation of inflammatory and epigenetics mechanism involved in cardiovascular complication of OSA patients compared with non OSA subjects, as well as the variation of epigenetic profiles in OSA patients after one year of high-adherence CPAP therapy.
2022-11-04 | GSE190164 | GEO
Project description:Genome wide DNA methylation profiling of obstructive sleep apnea (OSA) patients and healthy subjects. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in peripheral blood mononuclear cell samples. Samples included 8 normal subjects and 16 patients with obstructive sleep apnea syndrome.
2015-12-31 | GSE61463 | GEO
Project description:Genome wide DNA methylation profiling of obstructive sleep apnea (OSA) patients and healthy subjects. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in peripheral blood mononuclear cell samples. Samples included 8 normal subjects and 16 patients with obstructive sleep apnea syndrome. Bisulphite converted DNA from the 21 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2015-12-31 | E-GEOD-61463 | biostudies-arrayexpress
Project description:Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
2019-12-21 | GSE135917 | GEO
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index ≥ 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
2013-12-31 | GSE49800 | GEO
Project description:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.
2023-08-30 | GSE181270 | GEO
Project description:Therefore, we extended our investigation into OSA patients with long-term continuous positive airway pressure (CPAP) treatment, hypertension, or excessive daytime sleepiness (EDS) by analyzing whole-genome gene expression profiles of PBMC in three comparisons: (1) treatment-naïve moderate to very severe OSA patients versus subjects with primary snoring; (2) moderate to very severe OSA patients with hypertension or EDS versus those without hypertension or EDS, respectively; (3) treatment-naïve very severe OSA patients versus those receiving at least one year of adequate CPAP treatment. We analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients with long-term continuous positive airway pressure (CPAP) treatment (VSOC).
2015-12-31 | E-GEOD-75097 | biostudies-arrayexpress
Project description:To understand the molecular change occurring in the atria during obstructive sleep apnea, we have implemented a rat model of OSA involving the surgical implantation of a tracheal obstructive device, allowing the rats to remain conscious and free-roaming throughout 2 weeks of apnea administration. Rats were divided into severe and moderate apnea groups, receiving a 23 second or 13 second apneas per minute, respectively. The two-dimensional polyacrylamide gel electrophoresis (2D PAGE) of atrial homogenates to compare the dysregulations in the protein pattern in severe and moderate apnea when compared to control.
2019-02-21 | PXD011181 | Pride