ABSTRACT: Microarray gene expression profiles of peripheral blood mononuclear cells (PBMC) in patients with obstructive sleep apnea and primary snoring
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.
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
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.
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
Project description:Sleep Disordered Breathing (SDB) is associated with a wide range of physiological changes, likely due in part to the influence of hypoxemia during sleep on gene expression. We studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: the Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. We performed discovery analysis in two community-based studies: the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580) and the Framingham Offspring Study (FOS; N=571). Associations with false discovery rate (FDR) q-value<0.05 in one study were considered to have replicated if a p-value<0.05 was observed in the other study. Associations that replicated between cohorts, or with FDR q-value<0.05 in meta-analysis of the two studies, were carried forward for gene expression analysis in the blood of 15 participants from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial who had moderate or severe obstructive sleep apnea (OSA) and were studied before and after three months of treatment with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis based on all trait and cohort analyses. We identified 22 genes associated with SDB traits in both MESA and FHS. Of these, lower CD1D and RAB20 expressions were associated with lower avgO2 in MESA and FHS, and CPAP treatment increased their expression in HeartBEAT. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2, i.e. in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated in response to CPAP treatment (HeartBEAT).
Project description:Atherosclerosis is the pathological basis of cardiovascular disease. Obstructive sleep apnea aggravates atherosclerosis, and chronic intermittent hypoxia (CIH) as a prominent feature of obstructive sleep apnea plays an important role during the process of atherosclerosis. The mechanisms of CIH in the development of atherosclerosis remain unclear. The microarray was used to investigate differentially expressed mRNAs and long noncoding RNAs (lncRNAs) in aorta from five groups of ApoE-/- mice fed with a high-fat diet and exposed to various conditions: normoxia for 8 weeks, CIH for 8 weeks, normoxia for 12 weeks, CIH for 12 weeks, or CIH for 8 weeks followed by normoxia for 4 weeks.
Project description:Illumina microarray analysis of primary human B cell and peripheral blood mononuclear cell (PBMC) co-cultures stimulated with anti-IgM and superantigens for 3 days (BT) compared to the same co-cultures without stimualtion (BTNo).
Project description:Healthy young males (n=13) attended in this controlled laboratory experiment stimulating a workin week with reduced sleep. After baseline, the experimental group (n=9) were partially sleep deprived for 5 nights (time in bed 4 h/night) and had a recovery period of two nights (8 h/night). The control group (n= 4) spent the time in the same laboratory conditions but sleeping normally (8 h/night). RNA expression was detected in peripheral blood mononuclear cells (PBMC) taken in the morning after baseline (BL), sleep restriction (SR), and recovery (REC) periods.