Identification of key genes and immune infiltration modulated by CPAP in obstructive sleep apnea by integrated bioinformatics analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Fan C
PROVIDER: S-EPMC8445487 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCircadian rhythm disruption and immune infiltration are both closely associated with the development of Obstructive sleep apnea (OSA) disease and a variety of cardiovascular and neurological complications, but their interactions with OSA disease are not clear. In this study, we used bioinformatics to investigate the roles of circadian rhythm disruption and immune microenvironments in OSA.MethodsWe analyzed differential genes and their associated functional pathways in the circadian rhythm-associated OSA dataset, then regrouped OSA samples using the differential genes and explored differences in immune cell infiltration between the two different subgroups. Meanwhile, we used two machine learning algorithms to further define circadian rhythm-related signature genes and to explore the relationship between key genes and immune cell infiltration. Finally, we searched for the transcription factors of the key differential gene JUN.ResultsWe screened 15 circadian rhythm-related differential genes in the OSA-related dataset and further defined 3 signature genes by machine learning algorithms. Immunoassays showed a significant increase in resting mast cell infiltration and a decrease in monocyte infiltration in the OSA group. The results of our animal experiments also confirmed that the expression of these 3 key genes, as well as the immune cell infiltration, showed a trend consistent with the results of the bioinformatics analysis.ConclusionsIn conclusion, this study reveals the interaction between circadian rhythm disruption and immune infiltration in OSA, providing new insights into the potential pathogenesis of OSA.
| S-EPMC10758485 | biostudies-literature
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:BackgroundObstructive sleep apnea is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure (CPAP) reduces blood pressure, but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, we evaluated the effects of nocturnal supplemental oxygen and CPAP on markers of cardiovascular risk.MethodsWe conducted a randomized, controlled trial in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for obstructive sleep apnea with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an apnea-hypopnea index of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial pressure.ResultsOf 318 patients who underwent randomization, 281 (88%) could be evaluated for ambulatory blood pressure at both baseline and follow-up. On average, the 24-hour mean arterial pressure at 12 weeks was lower in the group receiving CPAP than in the control group (-2.4 mm Hg; 95% confidence interval [CI], -4.7 to -0.1; P=0.04) or the group receiving supplemental oxygen (-2.8 mm Hg; 95% CI, -5.1 to -0.5; P=0.02). There was no significant difference in the 24-hour mean arterial pressure between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis.ConclusionsIn patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of obstructive sleep apnea with CPAP, but not nocturnal supplemental oxygen, resulted in a significant reduction in blood pressure. (Funded by the National Heart, Lung, and Blood Institute and others; HeartBEAT ClinicalTrials.gov number, NCT01086800 .).
| S-EPMC4172401 | biostudies-literature
Project description:Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear.We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure.Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone.In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .).
| S-EPMC4138510 | biostudies-literature
Project description:Objective. Obstructive sleep apnea (OSA) decreases sleep spindle density and frequency. We evaluated the effects of continuous positive airway pressure (CPAP) treatment on different features of sleep spindles. Methods. Twenty OSA patients underwent two night polysomnographies in a diagnostic phase and one night polysomnography after 6 months of CPAP treatment. The control group comprised 20 healthy controls. Sleep spindles were analyzed by a previously developed automated method. Unilateral and bilateral spindles were identified in central and frontopolar brain locations. Spindle density and frequency were determined for the first and last half of the NREM time. Results. The density of bilateral central spindles, which did not change in the untreated OSA patients, increased towards the morning hours during CPAP treatment and in the controls. Central spindles did not become faster with sleep in OSA patients and the central spindles remained slow in the left hemisphere even with CPAP. Conclusion. CPAP treatment normalized spindle features only partially. The changes may be associated with deficits in thalamocortical spindle generating loops. Significance. This study shows that some sleep spindle changes persist after CPAP treatment in OSA patients. The association of these changes to daytime symptoms in OSA patients needs to be further evaluated.
| S-EPMC5312446 | biostudies-literature
Project description: Not available
| S-EPMC4285454 | biostudies-literature
Project description:PurposeCPAP is the "gold standard" treatment for obstructive sleep apnea (OSA). Current CPAP models have developed additional functions including automatic CPAP and pressure relief. However, CPAP adherence has not improved over the last three decades. Many patients in low-income countries cannot afford these CPAP devices. A novel simple CPAP device with a fixed pressure without pressure controller was developed.MethodsManual CPAP pressure titration was performed in 127 patients with OSA. Six patients with a titration pressure higher than 11 cmH2O and 14 patients who could not tolerate CPAP were excluded, leaving 107 participating in the following 2 studies. In study one, 54 of 107 patients were treated by both conventional fixed CPAP and simple CPAP in random order. In the second study, another 53 patients were treated by both autoCPAP in automatic function and simple CPAP in random order. Simple CPAP was fixed at 10 cmH2O, 8 cmH2O, and 6 cmH2O for patients whose titration pressure was between 9-10, 7-8, and ≤ 6 cmH2O, respectively. Conventional fixed CPAP device was set exactly the same as manual titration pressure.ResultsAll patients whose manual titration pressure ≤ 10 cmH2O were effectively treated by simple CPAP (AHI 40.7 ± 2.3 events/h before vs 2.5 ± 0.3 events/h after, p < 0.001). Patients expressed similar preferences for simple CPAP, autoCPAP, and conventional fixed CPAP (p > 0.05).ConclusionsWe conclude that a novel simple CPAP is an alternative treatment for most patients with OSA, which may widen access to CPAP therapy in the developing countries because of its low cost.
| S-EPMC10656318 | biostudies-literature
Project description:IntroductionObstructive sleep apnea (OSA) is a common medical condition with well-established morbidity and mortality. Continuous positive airway pressure (CPAP) is a highly effective treatment prescribed to most individuals with OSA that has documented poor adherence rate for a variety of reasons including claustrophobia and discomfort. CPAP desensitization is an effective, simple, and brief treatment shown to improve adherence rates to CPAP.MethodsA psychologist specializing in behavioral sleep medicine developed this module focused on teaching medical residents the techniques of CPAP desensitization. The educational activity was an interactive 45-minute seminar which included a didactic component followed by a case presentation and interactive role-play. A postseminar survey was used to evaluate the content of the workshop, as well as growth in awareness and perception of knowledge and skills with a pre- to postworkshop evaluation.ResultsIn a survey of 25 primary care and psychiatry residents and sleep medicine fellows, 92% of respondents indicated that the topic of CPAP barriers and CPAP desensitization was important. Ratings of self-reported knowledge and skills improved nearly one-third following the workshop. Qualitative feedback indicated the utility and enthusiasm learners had for this topic.DiscussionThe workshop on CPAP desensitization was a valuable tool that should be disseminated more widely to improve treatment adherence in the significant portion of the population that suffers from OSA which does not use adherence to positive airway pressure therapy. The workshop is applicable to other health professionals including medical students and nursing, social work, or psychology trainees.
| S-EPMC7499811 | biostudies-literature
Project description:Study objectivesUncertainty exists over whether continuous positive airway pressure (CPAP) treatment improves moderate to vigorous physical activity levels in those with obstructive sleep apnea. We aimed to determine effects of CPAP on moderate to vigorous physical activity among participants with co-occurring cardiovascular disease and obstructive sleep apnea.MethodsThe Sleep Apnea cardioVascular Endpoints (SAVE) trial recruited participants with confirmed cardiovascular disease history and obstructive sleep apnea, 45-75 years old. The 2,687 participants (1,346 randomized to CPAP plus usual care and 1,341 to usual care alone) were followed up for a mean of 3.7 years. Self-reported physical activity was recorded at baseline, 6, 24, and 48 months using the Godin-Shepard Leisure Time Exercise Questionnaire (LTEQ). We also determined effects on any limitation of physical activity reported on the physical functioning subscale of the 36-item short form questionnaire (SF-36) and proportions of participants reaching guideline recommended physical activity levels.ResultsAmong 2,601 participants with available data, those in the CPAP group reported significantly more physical activity compared to the usual care group, with approximately 20% higher reported moderate activities on the LTEQ during follow-up (adjusted mean 95% confidence interval) scores: 8.7, 7.5-9.9 vs 7.3, 6.1-8.5; P = .003). Those in the CPAP group also reported less limitation in physical activity (adjusted between-group difference in SF-36 physical functioning subscale score 1.66, 95% confidence interval 0.87-2.45; P < 0.001), and more reported sufficient levels of physical activity to meet recommendations.ConclusionsCPAP has positive effects on improving physical activity levels, consistent with long-term health benefits.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea to Prevent Cardiovascular Disease (SAVE); URL: https://clinicaltrials.gov/ct2/show/NCT00738179; Identifier: NCT00738179; and Registry: Australian New Zealand Clinical Trials Registry; Name: Sleep Apnea cardioVascular Endpoints study-An investigation of continuous positive airway pressure for the treatment of obstructive sleep apnea to prevent cardiovascular disease; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83062&isReview=true; Identifier: ACTRN12608000409370.
| S-EPMC7853210 | biostudies-literature
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress