The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells.
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ABSTRACT:
SUBMITTER: Haddad H
PROVIDER: S-EPMC8584070 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: We compared the density and duration of sleep spindles topographically in stage 2 and 3 of non-rapid eye movement sleep (N2 and N3) among adults diagnosed with Obstructive Sleep Apnea Syndrome (OSAS) and healthy controls. Materials and Methods: Thirty-one individuals with OSAS (mean age: 48.50 years) and 23 healthy controls took part in the study. All participants underwent a whole night polysomnography. Additionally, those with OSAS were divided into mild, moderate and severe cases of OSAS. Results: For N2, sleep spindle density did not significantly differ between participants with and without OSAS, or among those with mild, moderate and severe OSAS. For N3, post-hoc analyses revealed significantly higher spindle densities in healthy controls and individuals with mild OSAS than in those with moderate or severe OSAS. Last, in N2 a higher AHI was associated with a shorter sleep spindle duration. Conclusion: OSAS is associated with a significantly lower spindle density in N3 and a shorter spindle duration in N2. Our results also revealed that, in contrast to moderate and severe OSAS, the sleep spindle characteristics of individuals with mild OSAS were very similar to those of healthy controls.
| S-EPMC7947924 | biostudies-literature
Project description:PURPOSE: The aim of this study was to evaluate markers of systemic oxidative stress and antioxidant capacity in subjects with and without OSAS in order to investigate the most important factors that determine the oxidant-antioxidant status. METHODS: A total of 66 subjects referred to our Sleep laboratory were examined by full polysomnography. Oxidative stress and antioxidant activity were assessed by measurement of the derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidant capacity (BAP) in blood samples taken in the morning after the sleep study. Known risk factors for oxidative stress, such as age, sex, obesity, smoking, hypelipidemia, and hypertension, were investigated as possible confounding factors. RESULTS: 42 patients with OSAS (Apnea-Hypopnea index >15 events/hour) were compared with 24 controls (AHI<5). The levels of d-ROMS were significantly higher (p = 0.005) in the control group but the levels of antioxidant capacity were significantly lower (p = 0.004) in OSAS patients. The most important factors predicting the variance of oxidative stress were obesity, smoking habit, and sex. Parameters of sleep apnea severity were not associated with oxidative stress. Minimal oxygen desaturation and smoking habit were the most important predicting factors of BAP levels. CONCLUSION: Obesity, smoking, and sex are the most important determinants of oxidative stress in OSAS subjects. Sleep apnea might enhance oxidative stress by the reduction of antioxidant capacity of blood due to nocturnal hypoxia.
| S-EPMC3382594 | biostudies-other
Project description:BACKGROUND: Sleep-related disorders are among the important risk factors for neurovascular diseases. Obstructive sleep apnea syndrome (OSAS) is characterized by snoring, excessive daytime sleepiness, and insomnia. Our aim was to investigate the presence of glaucoma in patients with OSAS and to reveal vascular pathology related to the pathogenesis of glaucoma in those patients. PATIENTS AND METHODS: The study included 31 patients with OSAS and 25 control subjects. Orbital Doppler ultrasonography was used to determine the resistivity index (RI) in the ophthalmic artery and central retinal artery. All patients and controls underwent perimetric examination. RESULTS: The prevalence of glaucoma in the group of patients with OSAS was 12.9% (4/31); all of these 4 patients with glaucoma were in the "severe" OSAS group. No statistically significant difference was found between ophthalmic artery resistivity index (OARI), central retinal artery resistivity index (CRARI), and intraocular pressure (IOP) between patients and controls (p > 0.05). There was a positive correlation between OARI and mean defect (MD), CRARI and MD, and CRARI and loss variance (LV) values (p < 0.05). There was also a positive correlation between IOP and the apnea-hypopnea index (AHI) (p = 0.001). CONCLUSIONS: In patients with OSAS, a high prevalence was found and it is interesting to note that all of the four glaucoma patients were in the severe OSAS group. The positive correlation observed between IOP and AHI suggests that increased IOP values may reflect the severity of OSAS. The positive correlation between OARI and MD and also between CRARI and MD as well as LV suggests that visual field defects may be due to optic nerve perfusion defects and these field defects also increase as the RI increases.
| S-EPMC2082068 | biostudies-other
Project description:Obstructive sleep apnea syndrome (OSAS) and obesity go hand in hand in the majority of patients and both are associated with a systemic inflammation, immune disturbance and comorbidities such as cardiovascular disease. However, the unambiguous impact of OSAS and obesity on the individual inflammatory microenvironment and the immunological consequences of human monocytes has not been distinguished yet. Therefore, aim of this study was to investigate the impact of OSAS and obesity related factors on the inflammatory microenvironment by performing flow cytometric whole blood measurements of CD14/CD16 monocyte subsets in normal weight OSAS patients, patients with obesity but without OSAS, and patients with OSAS and obesity, compared to healthy donors. Moreover, explicitly OSAS and obesity related plasma levels of inflammatory mediators adiponectin, leptin, lipocalin and metalloproteinase-9 were determined and the influence of different OSAS and obesity related factors on cytokine secretion and expression of different adhesion molecules by THP-1 monocytes was analysed. Our data revealed a significant redistribution of circulating classical and intermediate monocytes in all three patient cohorts, but differential effects in terms of monocytic adhesion molecules CD11a, CD11b, CD11c, CX3CR1, CD29, CD49d, and plasma cytokine levels. These data were reflected by differential effects of OSAS and obesity related factors leptin, TNFα and hypoxia on THP-1 cytokine secretion patterns and expression of adhesion molecules CD11b and CD49d. In summary, our data revealed differential effects of OSAS and obesity, which underlines the need for a customized therapeutic regimen with respect to the individual weighting of these overlapping diseases.
| S-EPMC10764945 | biostudies-literature
Project description:Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by repeated episodes of upper airways collapse during the sleep. The following intermittent hypoxia triggers a state of chronic inflammation, which also interests the nervous system leading to neuronal damage and increased risk of cognitive impairment. Brain derived neurotrophic factor (BDNF) is a growth factor often associated with neuroplasticity and neuroprotection whose levels increase in several condition associated with neuronal damage. However, whether patients affected by OSAS have altered BDNF levels and whether such alteration may be reflective of their cognitive impairment is still controversial. Here we show that, when compared to healthy control volunteers, OSAS patients have increased serum levels of BDNF. Moreover, OSAS patients with the higher levels of BDNF also have reduced neurocognitive impairment as measured by The Montreal Cognitive Assessment (MoCA) questionnaire. Treatment with standard non-invasive mechanical ventilation (CPAP) also was able to ameliorate the level of cognitive impairment. Altogether our results indicate that BDNF levels represent a neuroprotective response to intermittent hypoxia in OSAS patients.
| S-EPMC6968866 | 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
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-κB 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.
2012-09-01 | GSE38792 | GEO
Project description:Obstructive sleep apnea syndrome (OSA) is associated with cardiovascular morbidity in adults and children. NF?B activity is enhanced in circulating monocytes of adults with OSA, that decreases following positive pressure therapy. OSA children's serum activates NF?B in a cell line. We hypothesized that OSA children's serum can activate NF?B in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NF?B in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls. Increased expression of NF?B classical subunits p65/p50 as well as major morphological changes occurred in cardiomyocytes following OSA's serum exposure. OSA children's serum induced NF?B activity as measured by p65 nuclear translocation in immortalized human CM and rat cardiomyocytes as well as dense immunostaining of the nucleus. Trypan blue and XTT assays showed that OSA sera induced CM apoptosis. We conclude that NF?B is systemically activated in cardiomyocytes, who also demonstrate decreased viability and contractility following exposure to OSA serum. It supports the hypothesis NF?B plays a role in the evolution of cardiovascular morbidity in OSA. It may support the search for new therapeutic interventions controlling NF?B activation in OSA.
| S-EPMC7747711 | biostudies-literature
Project description:Study objectiveAdenotonsillectomy is the recommended treatment for children with obstructive sleep apnea (OSA). Since adenoidectomy alone may be associated with significantly lower morbidity, mortality, and cost, we aimed to investigate whether adenoidectomy alone is a reasonable and appropriate treatment for children with OSA.MethodsFive-hundred fifteen consecutive children diagnosed with moderate-to-severe OSA (apnea-hypopnea index > 5) based on polysomnography and who underwent adenoidectomy or adenotonsillectomy were reevaluated after 17-73 months (mean 41) for residual or recurrent OSA using a validated questionnaire (Pediatric Sleep Questionnaire, PSQ). Failure of OSA resolution was defined as a positive mean PSQ score ≥ 0.33. Contribution of age, obesity, tonsil size, and OSA severity at baseline to adenoidectomy or adenotonsillectomy failure was examined.ResultsPositive PSQ score occurred in 15% of the entire sample and was not influenced by age or gender. No difference in failure rate was observed between adenoidectomy and adenotonsillectomy for children who were not obese with apnea-hypopnea index < 10 and had small tonsils (< 3). Children with apnea-hypopnea index ≥ 10 and/or tonsil size ≥ 3 showed a higher failure rate after adenoidectomy compared to adenotonsillectomy (20% versus 9.8%, p = 0.028).ConclusionsWe suggest that subjective, long term outcomes of adenoidectomy are comparable to those of adenotonsillectomy in non-obese children under 7 years old with moderately OSA and small tonsils. Hence, adenoidectomy alone is a reasonable option in some children. Future prospective randomized studies are warranted to define children who may benefit from adenoidectomy alone and those children in whom adenoidectomy alone is unlikely to succeed.
| S-EPMC4990952 | biostudies-literature
Project description:OBJECTIVE: To assess the macular retina and choroidal thickness change in patients with obstructive sleep apnea-hypopnea syndrome (OSAS) with no significant symptoms and pathological changes in the fundus using spectral domain-optical coherence tomography. METHODS: This prospective, observational case-control study consisted of 53 eyes of 53 patients with OSAS and 12 eyes of 12 age-matched controls. Macular and choroidal thicknesses were measured by optical coherence tomography. RESULTS: The foveal and nasal macular thicknesses were significantly different between four groups (P=0.001, P=0.016). The foveal thickness of the control group was significantly thinner than that of the severe group (P=0.000). The nasal macular thickness of the control group was significantly thinner than that of the severe group (P=0.008). A significant correlation was found between oxygen desaturation index (ODI) and macular center thickness (r=0.357, R(2)=0.127, P=0.004), with an ODI coefficient of 0.457 (P=0.004). Similarly, a significant correlation was found between ODI and nasal macular thickness (r=0.265, R(2)=0.070, P=0.033), with an ODI coefficient of 0.233 (P=0.033). The subfoveal choroidal thickness was significantly different among the groups (F=3.657, P=0.017). The subfoveal choroidal thickness of the severe group was significantly thinner than that of the control group, mild group, and moderate group (P=0.023, 0.006, and 0.036, respectively). The choroidal thickness 1 mm nasal to the fovea was significantly different between the groups after correcting for age and diopter (F=3.411, P=0.023). The choroidal thickness 1 mm nasal to the fovea was significantly thinner in the severe group compared with the control group and mild group (P=0.013 and 0.010, respectively). Choroidal thickness was significantly correlated with diopter (r=0.520, R(2)=0.270, P<0.001), with a coefficient of 0.327 (P<0.001), and with ODI (r=0.520, R(2)=0.165, P=0.001), with a coefficient of -0.370 (P=0.001). CONCLUSIONS: OSAS patients showed decreased foveal and nasal macular thickness, similar to the subfoveal and nasal choroidal thickness. These findings suggest that, because of intermittent hypoxia, OSAS might change the retinal and choroidal blood supply.
| S-EPMC3983631 | biostudies-literature