scholarly journals Identification of key genes and immune infiltration modulated by CPAP in Obstructive sleep apnea by integrated bioinformatics analysis

2021 ◽  
Author(s):  
yi Song ◽  
Cheng Fan ◽  
Shiyuan Huang ◽  
Chunhua Xiang ◽  
Tianhui An

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling. And continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remains elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 were downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255708
Author(s):  
Cheng Fan ◽  
Shiyuan Huang ◽  
Chunhua Xiang ◽  
Tianhui An ◽  
Yi Song

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling, and continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remain elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 was downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.


2021 ◽  
Vol 10 (7) ◽  
pp. 1387
Author(s):  
Raphael Boneberg ◽  
Anita Pardun ◽  
Lena Hannemann ◽  
Olaf Hildebrandt ◽  
Ulrich Koehler ◽  
...  

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Chien-Hung Chin ◽  
Chang-Chun Hsiao ◽  
Chia-Wei Liou ◽  
...  

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.


ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London

<b><i>Objective:</i></b> The purpose of this study was to evaluate the effects of nasal surgery on airflow characteristics in patients with obstructive sleep apnea (OSA) by comparing the alterations of airflow characteristics within the nasal and palatopharyngeal cavities. <b><i>Methods:</i></b> Thirty patients with OSA and nasal obstruction who underwent nasal surgery were enrolled. A pre- and postoperative 3-dimensional model was constructed, and alterations of airflow characteristics were assessed using the method of computational fluid dynamics. The other subjective and objective clinical indices were also assessed. <b><i>Results:</i></b> By comparison with the preoperative value, all postoperative subjective symptoms statistically improved (<i>p</i> &#x3c; 0.05), while the Apnea-Hypopnea Index (AHI) changed little (<i>p</i> = 0.492); the postoperative airflow velocity and pressure in both nasal and palatopharyngeal cavities, nasal and palatopharyngeal pressure differences, and total upper airway resistance statistically decreased (all <i>p</i> &#x3c; 0.01). A significant difference was derived for correlation between the alteration of simulation metrics with subjective improvements (<i>p</i> &#x3c; 0.05), except with the AHI (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Nasal surgery can decrease the total resistance of the upper airway and increase the nasal airflow volume and subjective sleep quality in patients with OSA and nasal obstruction. The altered airflow characteristics might contribute to the postoperative reduction of pharyngeal collapse in a subset of OSA patients.


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