scholarly journals Adhesion molecule gene variants and plasma protein levels in patients with suspected obstructive sleep apnea

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210732 ◽  
Author(s):  
Andrew J. Sandford ◽  
Amanda Ha ◽  
David A. Ngan ◽  
Loubna Akhabir ◽  
Aabida Saferali ◽  
...  
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.


Lung ◽  
2019 ◽  
Vol 197 (4) ◽  
pp. 459-464 ◽  
Author(s):  
N. T. Ayas ◽  
A. J. Hirsch Allen ◽  
N. Fox ◽  
B. Peres ◽  
M. Mehrtash ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ali Cengiz ◽  
Suat Konuk ◽  
Tuncer Tuğ

Aim. We aimed to investigate the relationship between serum pregnancy-associated plasma protein A (PAPP-A) levels and obstructive sleep apnea syndrome (OSAS). Materials and Method. 44 patients with OSAS and 44 healthy adults were included in this study. The participants having rheumatic or systemic inflammatory disease, advanced liver or kidney failure, diabetes, heart failure, hypertension, pregnancy, prerenal azotemia, known history of coronary artery disease, any pulmonary disease, rhinitis, or atopy, history of major trauma or surgery within the last six 6 months, and inhaled nasal or systemic corticosteroid use or other anti-inflammatory medications and those with <18 years of age were excluded. Serum PAPP-A levels were determined by the Elisa method with the immune sandwich measuring method. Statistical analysis of the study was performed with SPSS 17.0 statistical analysis package program, and p<0.05 was considered as significant. Results. Serum PAPP-A levels of patients with OSAS (2.350 ng/ml (0.641–4.796)) were significantly higher (p<0.001) when compared with healthy controls (0.971 ng/ml (0.109–2.679)). There was a statistically significant difference in serum PAPP-A levels between groups of OSAS patients according to the classification of OSAS severity. Between the groups of patients with OSAS, serum levels of PAPP-A in moderate group was significantly higher when compared with severe OSAS group (p<0.001). There was positive correlations between PAPP-A levels and night minimum (p=0.042,  r=0.309), and average oxygen levels (p=0.006,  r=0.407). There was a negative correlation between PAPP-A levels and AHI (p=0.002,  r=−0.460). Conclusion. Higher PAPP-A levels in OSAS patients that were found in this study show inflammatory component in OSAS.


2018 ◽  
Vol 314 (6) ◽  
pp. H1160-H1168 ◽  
Author(s):  
Sara L. Bober ◽  
John Ciriello ◽  
Douglas L. Jones

Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and β1-adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally on parasympathetic activation. Enhanced atrial vulnerability was accompanied by heightened electrophysiological responses of the atrial myocardium to carbachol and isoproterenol, dampened responses to propranolol, and increased atrial M2 receptor protein levels.


2017 ◽  
Vol 14 (1) ◽  
pp. 37-40
Author(s):  
E M Elfimova ◽  
A V Rvacheva ◽  
M I Tripoten ◽  
O V Pogorelova ◽  
T V Balakhonova ◽  
...  

Objective. To evaluate the effect of antihypertensive therapy (AHT) and CPAP therapy on inflammatory and endothelial dysfunction markers levels in patients with severe obstructive sleep apnea (OSA) syndrome in association with arterial hypertension (AH). Materials and methods. The study included 43 male patients with severe OSA syndrome (Apnea-Hypopnea Index 52.4 [46.1; 58.6]) and AH (systolic blood pressure 144.0 [142.0; 156.0] mm Hg, diastolic blood pressure 90.9 [88.3; 93.5] mm Hg). Treatment with angiotensin-converting enzyme inhibitors, calcium antagonists, and thiazide-like diuretics was performed till target BP level measured with Korotkoff method was achieved. The patients who had reached target BP level (BP≤140/90 mm Hg) were randomized into two groups: group 1 included 23 patients who continued taking the AHT, group 2 included 22 patients who continued taking the AHT to which CPAP therapy was added. Peripheral blood lymphocyte immunophenotyping, cytokine panel test (IL-1β, IL-6, tumor necrosis factor a, IL-2Ra, sCD40L), adhesion molecule analysis (ICAM-1, VCAM-1), thromboxane B2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1a), and endothelin-1 levels in blood serum were evaluated at admission, after target BP level achievement (2nd visit) and after 3 months of AHT or AHT+CPAP therapy (3rd visit). Flow-mediated dilation of brachial artery was assessed using reactive hyperemia test by D.Celermajer. Results. Against the background of combined AHT the target BP level was achieved by 95% of patients. After target BP level achievement a significant decrease of IL-1β -0.16 [-0.5; 0], p=0.000 level and number of CD50+ cells (lymphocytes with inter-cellular adhesion molecule ICAM-3) from 2158.5 [1884.7; 2432.3] to 1949.6 [1740.9; 2158.3], p=0.050 were observed in patients with severe OSA associated with AH. There were no significant changes in vascular endothelial function observed in patients taking only AHT. Significant decrease of fibrinogen (-0.3 [-0.4; -0.1], p=0.002) and homocystein (-2.03 [-3.8; -0.2], p=0.03) levels was observed in patients taking both AHT and CPAP therapy. Conclusion. The combination of AHT and CPAP therapy in patients with severe OSA and AH not only allows reaching the target BP level but also leads to inflammatory and endothelial dysfunction markers levels decrease.


Author(s):  
GÖZDE DEMİRCİ ◽  
ADİL ZAMANİ ◽  
ŞEBNEM YOSUNKAYA ◽  
İBRAHİM KILINÇ

Background/aim: Obstructive sleep apnea (OSA) is associated with serious cardio-metabolic risks. Early diagnosis and treatment compliance are important. For this purpose, research is being carried out on biomarkers associated with the pathogenesis of the disease. We aimed to investigate whether serum S100A12 and S100B proteins could be used as biochemical markers in OSA patients to determine disease presence and severity. Materials and Methods: A total of 60 (16 women, 44 men) patients with OSA and 50 (20 women, 30 men) controls were enrolled in this cross-sectional study. Each subject included in the study underwent full-night polysomnography (PSG). The presence and severity of OSA was assessed by the apnea?hypopnea index (AHI). In the OSA group, 17-cases were mild, 18 were moderate, and 25 were severe. The serum levels of S100A12 and S100B were measured using the enzyme-linked immunosorbent assay (ELISA) technique. These protein levels were compared using the Student?s t-test in the patient and control groups. Spearman's rho correlation coefficients and corresponding p-values were calculated to determine the correlations between these protein levels and polysomnographic parameters. For evaluating the association between OSA and biomarkers, as well as possible confounding factors with S100A12 and S100B, we employed multiple linear regression analyses for the patients with OSA. Results: Serum levels of S100A12 and S100B were higher in patients than controls (p=0.01 and p=0.005, respectively), and a significant correlation was determined between S100A12 and S100B values and AHI (p=0.0001; p=0.0001), sleep time with SpO2< 90% (p=0.032; p=0.01), minimum SpO2 during sleep (p=0.019; p=0.007), and oxygen desaturation index ODI (p=0.001; p=0.0001). In the linear regression analysis, AHI was independently related with both S100A12 (p<?0.0001) and S100B (p=?0.011). Receiving operating curves (ROC) identified patients with OSA: AUC for S100A12=0.643; AUC for S100B=0.655 (p<0.05). Conclusion: Serum levels of S100B and S100A proteins have high diagnostic performance in OSA and are independent predictors of OSA presence and severity.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A67-A67
Author(s):  
A Gabryelska ◽  
M Sochal ◽  
S Turkiewicz ◽  
P Bialasiewicz

Abstract Introduction Obstructive sleep apnea (OSA) is a chronic condition that is characterized by intermittent hypoxia. Key regulator of oxygen metabolism is hypoxia inducible factor (HIF), which consists of oxygen sensitive subunit and continuously produced subunit. Circadian clock is composed of set of genes, which function as activators - CLOCK and BMAL 1, who similarly to HIF are basic helix-loop-helix-PER-ARNT-SIM transcription factors. Therefore, the aim of the study was to assess the relationship between HIF-1alpha, HIF-1beta, CLOCK, BMAL1 and polysomnography (PSG) variables in healthy individuals and severe OSA patients. Methods The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI&lt;5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. HIF-1alpha, HIF-1beta, CLOCK and BMAL1 protein concertation measurements were performed using ELISA. Results Significant difference was observed in the following protein measurements between study groups: evening and morning HIF-1 (p=0.020 and p=0.043, respectively), evening HIF-1alpha (p=0.047), evening and morning CLOCK (p=0.037 and p=0.019, respectively) and morning BMAL1 (p=0.016). No differences were observed between morning and evening protein levels in both groups. Evening HIF-1beta corraleted with evening CLOCK and morning BMAL1 (R=0.511, p=0.21 and R=0.594, p=0.006, respectively), while morning HIF-1 with evening BMAL1 (R=474, p=0.35). Furthermore, evening and morning HIF-1 correlated with evening BMAL1 (R=564, p=0.010 and R=0.689, p=0.001, respectively). Additionally, morning CLOCK and BMAL1 correlated with AHI (R=0.510, p=0.022 and R=0.560, p=0.010, respectively) and desaturation index (R=0.487, p=0.209 and R=0.570, p=0.009, respectively). Conclusion There is significant correlation between both subunits of HIF-1 protein and circadian clock proteins: CLOCK and BMAL1, which further correlate with increased disease severity. This suggests OSA patients are in risk of circadian clock disruption due to present hypoxia. Support The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931.


Author(s):  
Dong-Kyu Kim ◽  
Byeong Chan Lee ◽  
Ki Joon Park ◽  
Gil Myeong Son

Objective: Chronic rhinosinusitis (CRS) with nasal polyp (wNP) is a more severe inflammatory form of CRS that often coexists with obstructive sleep apnea (OSA). However, little is known the relationship between OSA and immunologic profile on patients with CRSwNP. We aimed to investigate the immune profile of patients with CRSwNP according to OSA severity.Methods: This study included 63 patients with CRSwNP and nine control subjects. Protein levels of inflammatory mediators were determined using multiplex immunoassay. All patients underwent standard polysomnography.Results: We found that, in patients with eosinophilic CRSwNP (ECRSwNP), IL-6 and CXCL-1 (type 1 immune-related markers) were upregulated in cases of moderate-to-severe OSA. Additionally, IL-4, IL-13, CCL-11, CCL-24 (type 2 immune-related markers), and IL-17A (type 3 immune-related marker) were increased in patients with moderate-to-severe OSA. Though there were no significant differences in type 1, 2, or 3 immune-related markers among patients with non-eosinophilic CRSwNP (NECRSwNP) according to the severity of OSA, TGF-


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