scholarly journals 0170 Association of HIF-1 Alpha and Beta Subunits with Clock and BMAL1 Proteins in Obstructive Sleep Apnea Patients

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A67-A67
Author(s):  
A Gabryelska ◽  
M Sochal ◽  
S Turkiewicz ◽  
P Bialasiewicz
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Hypoxia Inducible Factor ◽  
Study Groups ◽  
Oxygen Metabolism ◽  
Apnea Hypopnea Index ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Significant Difference

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<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.

scholarly journals Relationship between HIF-1 and Circadian Clock Proteins in Obstructive Sleep Apnea Patients—Preliminary Study

2020 ◽  
Vol 9 (5) ◽  
pp. 1599 ◽  
Author(s):  
Agata Gabryelska ◽  
Marcin Sochal ◽  
Szymon Turkiewicz ◽  
Piotr Białasiewicz
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Protein Level ◽  
Hypoxia Inducible Factor ◽  
Apnea Hypopnea Index ◽  
Clock Proteins ◽  
Obstructive Sleep ◽  
Healthy Control ◽  
Circadian Clock Proteins

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and associated with the disruption of circadian rhythm. The study aimed to assess the relationship between hypoxia-inducible factor (HIF) subunits, circadian clock proteins, and polysomnography (PSG) variables, in healthy individuals and severe OSA patients. The study included 20 individuals, who underwent PSG and were divided into severe OSA group (n = 10; AHI ≥ 30) and healthy control (n = 10; AHI < 5) based on apnea-hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. HIF-1α, HIF-1β, BMAL1, CLOCK, CRY1, and PER1 protein concertation measurements were performed using ELISA. In a multivariate general linear model with the concentration of all circadian clock proteins as dependent variables, evening HIF-1α protein level was the only significant covariant (p = 0.025). Corrected models were significant for morning and evening PER1 (p = 0.008 and p = 0.006, respectively), evening (p = 0.043), and evening BMAL protein level (p = 0.046). In corrected models, evening HIF-1α protein level had an influence only on the evening PER1 protein level. Results suggest that OSA patients are at risk for developing circadian clock disruption. This process might be mediated by subunit α of HIF-1, as its increased protein level is associated with overexpression of circadian clock proteins.

scholarly journals P060 Hypoxia-induced overexpression of Rev-Erb-alpha and NPAS2 proteins in obstructive sleep apnea patients - possible mechanism of DM2 development

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A41-A41
Author(s):  
F Karuga ◽  
S Turkiewicz ◽  
M Ditmer ◽  
M Sochal ◽  
P Białasiewicz ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Serum Protein ◽  
Protein Level ◽  
Control Group ◽  
Apnea Hypopnea Index ◽  
Orphan Nuclear Receptor ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Significant Difference

Abstract Circadian clocks are endogenous coordinators of 24-hour behavioral and molecular rhythms, which disruption may be caused by obstructive sleep apnea (OSA). It is composed of a set of genes, function as activators (CLOCK, BMAL) or repressors (PER, CRY). Neuronal PAS Domain Protein 2 (NPAS2) can substitute CLOCK in its function. Orphan nuclear receptor (Rev-Erb-α) is another protein supporting the CLOCK-BMAL1 complex, forming the loop which helps to regulate their expression. There are studies suggesting the significant influence of circadian disruption mediated via NPAS2 and Rev-Erb-α on DM2 development. The aim of the study was to determine the role of NPAS2 and Rev-Erb-α in DM2 for OSA patients. All participants underwent polysomnography (PSG) examination. Based on apnea-hypopnea index accompanied by clinical data the recruited individuals (n=40) were assigned to one from 3 groups: OSA (severe OSA, no DM2; n=17), DM2 (severe OSA + DM2; n=7) and control group (no OSA, no DM2; n=16). Serum protein levels of Rev-Erb-α and NPAS2 were assessed with ELISA immunoassay. Analysis between the groups revealed the statistically significant difference only in NPAS2 protein level (p=0.037). Further post-hoc analysis revealed significant differences between OSA and the control group (p=0.017). Moreover, a statistically significant correlation between AHI and NPAS2 serum protein level was observed (r=-0.478, p=0.002). NPAS2 protein levels are associated with a number of apneas and hypopneas during the REM phase of sleep and might have a significant role in the development of OSA complications. However, further studies are needed to understand its role.

scholarly journals Disruption of Circadian Rhythm Genes in Obstructive Sleep Apnea Patients—Possible Mechanisms Involved and Clinical Implication

2022 ◽  
Vol 23 (2) ◽  
pp. 709
Author(s):  
Agata Gabryelska ◽  
Szymon Turkiewicz ◽  
Filip Franciszek Karuga ◽  
Marcin Sochal ◽  
Dominik Strzelecki ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Hypoxia Inducible Factor ◽  
Oxygen Metabolism ◽  
Neurological Complications ◽  
Upper Airways ◽  
Strong Base ◽  
Vast Number ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is a chronic condition characterized by recurrent pauses in breathing caused by the collapse of the upper airways, which results in intermittent hypoxia and arousals during the night. The disorder is associated with a vast number of comorbidities affecting different systems, including cardiovascular, metabolic, psychiatric, and neurological complications. Due to abnormal sleep architecture, OSA patients are at high risk of circadian clock disruption, as has been reported in several recent studies. The circadian clock affects almost all daily behavioral patterns, as well as a plethora of physiological processes, and might be one of the key factors contributing to OSA complications. An intricate interaction between the circadian clock and hypoxia may further affect these processes, which has a strong foundation on the molecular level. Recent studies revealed an interaction between hypoxia-inducible factor 1 (HIF-1), a key regulator of oxygen metabolism, and elements of circadian clocks. This relationship has a strong base in the structure of involved elements, as HIF-1 as well as PER, CLOCK, and BMAL, belong to the same Per-Arnt-Sim domain family. Therefore, this review summarizes the available knowledge on the molecular mechanism of circadian clock disruption and its influence on the development and progression of OSA comorbidities.

Aerodynamics Analysis of the Impact of Nasal Surgery on Patients with Obstructive Sleep Apnea and Nasal Obstruction

ORL ◽  
2021 ◽  
pp. 1-8
Author(s):  
Lifeng Li ◽  
Demin Han ◽  
Hongrui Zang ◽  
Nyall R. London
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nasal Obstruction ◽  
Upper Airway ◽  
Apnea Hypopnea Index ◽  
Nasal Surgery ◽  
Subjective Sleep Quality ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
The Impact

<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.

scholarly journals Clinical and Polysomnographic Characteristics of Patients with Extreme Obstructive Sleep Apnea, AHI > 100: A Case-Control Study

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Forogh Soltaninejad ◽  
Negarsadat Neshat ◽  
Mehrzad Salmasi ◽  
Babak Amra
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
Study Results ◽  
Significant Difference ◽  
Severe Manifestation ◽  
The Mean ◽  
Nocturnal Polysomnography ◽  
Control Study

Background: Severe obstructive sleep apnea (OSA), defined by apnea-hypopnea index (AHI) as more than 30 events per hour, was previously related to more comorbidity. However, limited studies separated the patients with AHI > 100 from those with a less severe manifestation of the disease. Objectives: The current study aimed at describing the characteristics of this subgroup and comparing them with less severe conditions. Methods: A retrospective analysis was conducted on 114 patients with OSA. Nocturnal polysomnography was used to diagnose severe OSA. Patients were categorized into two groups: (1) 60 < AHI < 100 (very severe OSA), (2) AHI ≥ 100 (extreme OSA). Demographic, medical history, and polysomnographic variables were evaluated and compared between the two groups. Results: Extreme OSA was diagnosed in 19 patients, the mean body mass index (BMI) was significantly higher in this group (39.26 ± 5.93 vs. 35.68 ± 6.45 kg/m2, P = 0.025). They also had lower minimal O2 saturation (65.68 ± 10.16 vs. 74.10 ± 8.74, P = 0.003) and more time with < 90% O2 saturation (T < 90%) (81.78 ± 22.57 vs. 58.87 ± 33.14, P = 0.01). OHS prevalence was significantly higher in the group with extreme OSA (P = 0.04). The most frequent comorbidity was hypertension, with an incidence of 60.5%, for the extreme group, although there was no significant difference between the two groups in terms of clinical associations. Conclusions: The current study results suggested that greater BMI and lower minimal O2 saturation, as well as increased T < 90%, were associated with extreme OSA, although no differences were observed in the associated diseases between the compared groups.

scholarly journals Severity of obstructive sleep apnea (OSA) in 382 Han and Uyghur patients with sleep disorders

2018 ◽  
Vol 01 (02) ◽  
pp. 163-169
Author(s):  
Aman Gul ◽  
Nassirhadjy Memtily ◽  
Aikeranmu Aihemaiti ◽  
Amir Abdukadir ◽  
Palidan Wushuer
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Race And Ethnicity ◽  
Impact Factors ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
Adults And Children ◽  
Respiratory Disturbance ◽  
Distinctive Difference

Objective: Race and ethnicity may impact the prevalence and severity of Obstructive Sleep Apnea (OSA) in adults and children. In this study, we aim to investigate the ethnologic influence on OSA severity between Han and Uyghur OSA patients in Xinjiang, China.Methods: We enrolled total of 382 (205 Han and 177 Uyghur) patients diagnosed with OSA with apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) [Formula: see text] 5. During admission, the severity of OSA was evaluated by polysomnography (PSG).Results: From demographic characteristics of enrolled patients, we found that there was no significant difference in sex, age, BMI, and neck circumference between two study populations. Uyghur OSA patients had longer sleep latency, longer REM sleep and N3 stage, but shorter N1 phase than Han OSA patients. AHI and apnea RDI level, but not hypopnea RDI, were evidently higher in Han patients compared with Uyghur patients. There was no distinctive difference between two ethnic populations in average and minimum peripheral capillary oxygen saturation (SaO2) level.Conclusion: Better understanding of impact factors encompassing ethnicity may help improve OSA diagnosis accuracy, management and treatment for patients in Xinjiang.

scholarly journals Do the turbinates play an important role in obstructive sleep apnea syndrome? – Our experience

2016 ◽  
Vol 6 (22) ◽  
pp. 93-98
Author(s):  
Nicoleta Dumitrescu ◽  
Raluca Enache ◽  
Codrut Sarafoleanu
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Apnea Hypopnea Index ◽  
Nasal Airflow ◽  
Nasal Surgery ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
Apnea Syndrome

Abstract BACKGROUND. Nasal obstruction may trigger obstructive sleep apnea syndrome (OSAS) and it is considered to be a cofactor in its pathophysiology. However, the relation between cause and effect still remains a matter of debate. MATERIAL AND METHODS. 18 patients diagnosed with chronic hypertrophic rhinitis and obstructive sleep apnea syndrome were included in the present study. All patients underwent nasal surgery as the single treatment for their sleep breathing disorders. Rhinomanometric (total nasal airflow, logReff, logVR) and polygraphic parameters (apnea-hypopnea index - AHI, snore flags index – SFI) were evaluated pre- and 2 months postoperatively. RESULTS. There was a statistically significant difference between the values of the preoperative and postoperative total nasal airflow (p-value<0.0001). In case of AHI, there was a decrease in its value from 31.56 preoperatively to 30.03 postoperatively, but the difference was not statistically significant (p=0.937). The SFI, on the other hand, presented a significant decrease (p=0.05), from a mean value of 93.15 preoperatively to 56.02 after the surgery. The correlation of the total nasal airflow with AHI and SFI, revealed that nasal surgery had an important impact upon snoring characteristics (r=0.24) and less upon OSAS severity (r=0.21). CONCLUSION. The nasal cavity obstruction contributes less to OSAS, but still represents a disorder that needs to be corrected in case of such patients. Turbinates reduction surgery may be applied in the treatment of OSAS and combined with palate and/or tongue surgery.

scholarly journals Serum S100A12 and S100B Proteins are Independent Predictors of the Presence and Severity of Obstructive Sleep Apnea

2019 ◽  
Author(s):  
GÖZDE DEMİRCİ ◽  
ADİL ZAMANİ ◽  
ŞEBNEM YOSUNKAYA ◽  
İBRAHİM KILINÇ
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Linear Regression ◽  
Linear Regression Analysis ◽  
Treatment Compliance ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apnea Hypopnea Index ◽  
Protein Levels ◽  
Obstructive Sleep

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.

Robotic Modification of Epiglottis Trimming in the Treatment of Obstructive Sleep Apnea

2021 ◽  
pp. 019459982110646
Author(s):  
Mehmet Ali Babademez ◽  
Fatih Gul ◽  
Kadir Sinasi Bulut ◽  
Mecit Sancak ◽  
Saliha Kusoglu Atalay
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Tertiary Hospital ◽  
Apnea Hypopnea Index ◽  
Complete Relief ◽  
Sleep Endoscopy ◽  
Drug Induced ◽  
Drug Induced Sleep Endoscopy ◽  
Obstructive Sleep ◽  
Significant Difference

Objective With the widespread use of drug-induced sleep endoscopy, it has been suggested that epiglottis pathologies are present at high rates in patients with sleep apnea. The aim of our study was to evaluate the efficacy of trimming the curled-inward epiglottis as an updated surgical technique in patients with omega epiglottis. Study Design Retrospective study. Setting Tertiary hospital. Methods Among the 283 patients with epiglottis pathology, 21 with isolated omega-shaped epiglottis (age, 33-53 years) fulfilled the inclusion criteria between May 2016 and April 2019. Drug-induced sleep endoscopy was used to detect epiglottic collapse compressed by the lateral parts during inspiration. An epiglottoplasty technique was applied as single-level sleep surgery in patients with an isolated omega-shaped epiglottis. The medical data were also reviewed. Results The mean pre- and postoperative total apnea-hypopnea index (AHI) scores were 27.89 and 10.58, respectively, and this difference was statistically significant ( P < .001). There was a statistically significant difference between the pre- and postoperative supine AHI scores (27.02 vs 10.48, P < .001). Surgical success, defined as AHI <20 and a decrease in AHI by 50%, was documented in 85.71% of patients (18/21), and 12 patients found complete relief from obstructive sleep apnea symptoms (AHI <5); the cure rate was 38.09% (8/21). Conclusion Trimming the curled-inward epiglottis may represent an excellent option for epiglottis surgery in patients with obstructive sleep apnea by being less invasive than techniques currently in use.

MRI evaluation of cerebral metabolic rate of oxygen (CMRO2) in obstructive sleep apnea

2022 ◽  
pp. 0271678X2110710
Author(s):  
Pei-Hsin Wu ◽  
Ana E Rodríguez-Soto ◽  
Andrew Wiemken ◽  
Erin K Englund ◽  
Zachary B Rodgers ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Blood Flow Rate ◽  
Oxygen Metabolism ◽  
Breath Hold ◽  
Sagittal Sinus ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
Venous Oxygen Saturation ◽  
Brain Oxygen Metabolism

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO2 via Fick’s Principle. Enrolled subjects were classified based on their apnea-hypopnea indices into OSA (N = 31) and non-sleep apnea reference subjects (NSA = 21), and further compared with young healthy subjects (YH, N = 10). OSA and NSA subjects were matched for age and body mass index. CMRO2 was lower in OSA than in the YH group during normal breathing (105.6 ± 14.1 versus 123.7 ± 22.8 μmol O2/min/100g, P = 0.01). Further, the fractional change in CMRO2 in response to a breath-hold challenge was larger in OSA than in the YH group (15.2 ± 9.2 versus 8.5 ± 3.4%, P = 0.04). However, there was no significant difference in CMRO2 between OSA and NSA subjects. The data suggest altered brain oxygen metabolism in OSA and possibly in NSA as well.

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