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.

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 Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

2021 ◽  
Vol 22 (22) ◽  
pp. 12536
Author(s):  
Szymon Turkiewicz ◽  
Marta Ditmer ◽  
Marcin Sochal ◽  
Piotr Białasiewicz ◽  
Dominik Strzelecki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Chronic Inflammation ◽  
Cellular Senescence ◽  
Molecular Mechanisms ◽  
Telomere Shortening ◽  
Age Related ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

scholarly journals Obstructive sleep apnea syndrome and cognitive impairment: effects of CPAP

2011 ◽  
Vol 2 (4) ◽  
pp. 209
Author(s):  
Alessandra Giordano ◽  
Alessandro Cicolin ◽  
Roberto Mutani
Keyword(s):  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Executive Functions ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Muscular Activity ◽  
Upper Airways ◽  
Obstructive Sleep ◽  
Apnea Syndrome

Obstructive Sleep Apnea Syndrome (OSAS) is a sleep disorder characterised by repetitive episodes of upper airway obstruction (apnea) or reduced airflow (hypopnoea) despite persistent respiratory effort. Apnea is defined as the cessation of breathing for at least 10 seconds during sleep, while hypopnoea is defined as at least 30% reduction in airflow for 10 seconds associated with oxygen desaturation and sleep fragmentation. The presence in the general population is about 4%. The principal symptoms are: excessive daytime sleepiness (EDS), snoring, dry throat, morning headache, night sweats, gastro-esophageal reflux, and increased blood pressure.Long term complications can be: increased cardio-cerebrovascular risk and cognitive impairment such as deficiency in attention, vigilance, visual abilities, thought, speech, perception and short term memory.Continuous Positive Airway Pressure (CPAP) is currently the best non-invasive therapy for OSAS.CPAP guarantees the opening of upper airways using pulmonary reflexive mechanisms increasing lung volume during exhalation and resistance reduction, decreasing electromyografical muscular activity around airways.The causes of cognitive impairments and their possible reversibility after CPAP treatment have been analysed in numerous studies. The findings, albeit controversial, show that memory, attention and executive functions are the most compromised cognitive functions.The necessity of increasing the patient compliance with ventilotherapy is evident, in order to prevent cognitive deterioration and, when possible, rehabilitate the compromised functions, a difficult task for executive functions.

scholarly journals Adherence to the Mediterranean lifestyle is inversely associated with insomnia presence and severity: cross-sectional analysis in obstructive sleep apnea patients

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Ioanna Kechribari ◽  
Meropi Kontogianni ◽  
Michael Georgoulis ◽  
Kallirroi Lamprou ◽  
Antonia Kalogera ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Healthy Lifestyle ◽  
Well Being ◽  
Sleep Habits ◽  
Upper Airways ◽  
Lifestyle Habits ◽  
Obstructive Sleep ◽  
The Mediterranean ◽  
Insomnia Symptoms

AbstractInsomnia is the most prevalent sleep disorder and frequently co-occurs with obstructive sleep apnea (OSA), a chronic disease characterized by repetitive pauses of breathing during sleep due to obstructions of the upper airways. The link between lifestyle and sleep quantity and quality is an area of intensive research, however data exploring associations between lifestyle habits and insomnia symptoms are still scarce. The aim of the present study was to investigate the potential association between the level of adherence to the Mediterranean lifestyle (ML), a healthy lifestyle pattern incorporating the prudent Mediterranean diet, adequate physical activity and healthy sleep habits, and insomnia presence and severity. The study sample consisted of 243 adult patients with polysomnography-diagnosed OSA. Participants’ insomnia-related disorders were evaluated through the Athens Insomnia Scale (AIS), an 8-item index ranging from 0 (absence of any sleep-related problem) to 24 (severe degree of insomnia); AIS values of > 6 were used to establish the diagnosis of insomnia. All patients were evaluated with regard to anthropometric indices and lifestyle habits, and adherence to the ML was estimated through the MEDLIFE index, a 28-item index ranging from 0 to 28, with higher values indicating greater proximity to the healthy lifestyle of the Mediterranean region. An inverse correlation was observed between the MEDLIFE index and total AIS (rho = -0.22, p = 0.001), as well as most individual components of AIS, including difficulty in sleep induction (rho = -0.14, p = 0.03), awakenings during the night (rho = -0.2, p = 0.008), short sleep duration (rho = -0.16, p = 0.01), low quality of sleep (rho = -0.13, p = 0.05), low well-being during the day (rho = -0.16, p = 0.02), and low functioning capacity during the day (rho = -0.15, p = 0.02). Patients with insomnia (AIS > 6), compared to those without (AIS ≤ 6), exhibited lower MEDLIFE index values [13 (11–15) vs. 14 (12–15), P = 0.002], had more severe OSA as assessed by the apnea-hypopnea index (AHI) [55 (24–87) vs. 35 (17–57) events/hour, P < 0.001] and tended to have higher body mass index (BMI) [35.0 (30.6–39.7) vs. 32.4 (29.5–38.6) kg/m2, P = 0.06]. According to logistic regression analysis, MEDLIFE index was inversely associated with the presence of insomnia (OR: 0.89, 95%CI: 0.80–0.99, P = 0.04) after adjustment for age, sex, smoking, BMI, daily energy intake and AHI. In conclusion, a higher adherence to the ML is inversely associated with insomnia presence and severity in patients with obstructive sleep apnea. Future research should assess whether this association applies in other samples, as well as whether the ML could be an efficient therapeutic tool alleviating or treating insomnia symptoms.

scholarly journals Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer

2018 ◽  
Vol 315 (4) ◽  
pp. R669-R687 ◽  
Author(s):  
Imre Hunyor ◽  
Kristina M. Cook
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Inflammatory Responses ◽  
Hypoxia Inducible Factor ◽  
Small Animal ◽  
Molecular Pathways ◽  
Significant Heterogeneity ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, there is significant heterogeneity in published methods for modeling hypoxic conditions, which are often lacking in physiological relevance. This is particularly important for studying key transcriptional mediators of the hypoxic and inflammatory responses such as hypoxia-inducible factor (HIF) and NF-κB. The relationship between HIF, the molecular clock, and circadian rhythm may also contribute to cancer risk in OSA. Building accurate in vitro models of intermittent hypoxia reflective of OSA is challenging but necessary to better elucidate underlying molecular pathways.

scholarly journals A Pharyngoplasty with a Dorsal Palatal Flap Expansion: The Evaluation of a Modified Surgical Treatment Method for Obstructive Sleep Apnea Syndrome—A Preliminary Report

2021 ◽  
Vol 10 (16) ◽  
pp. 3746
Author(s):  
Ewa Olszewska ◽  
Piotr Fiedorczuk ◽  
Adam Stróżyński ◽  
Agnieszka Polecka ◽  
Ewa Roszkowska ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Oxygen Saturation ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Apnea Hypopnea Index ◽  
Upper Airways ◽  
Sleep Study ◽  
Obstructive Sleep ◽  
Apnea Syndrome

Surgical techniques for obstructive sleep apnea syndrome (OSAS) constantly evolve. This study aims to assess the effectiveness and safety of a new surgical approach for an OSAS pharyngoplasty with a dorsal palatal flap expansion (PDPFEx). A total of 21 participants (mean age 49.9; mean BMI 32.5) underwent a type III sleep study, an endoscopy of the upper airways, a filled medical history, a visual analog scale for snoring loudness, an Epworth Sleepiness Scale, and a Short Form Health Survey-36 questionnaire. A follow-up re-evaluation was performed 11 ± 4.9 months post-operatively. The study group (4 with moderate, 17 with severe OSAS) showed an improvement in all measured sleep study characteristics (p < 0.05), apnea-hypopnea index (pre-median 45.7 to 29.3 post-operatively, p = 0.009, r = 0.394), oxygen desaturation index (pre-median 47.7 and 23.3 post-operatively, p = 0.0005, r = 0.812), mean oxygen saturation (median 92% pre-operatively and median 94% post-operatively, p = 0.0002, r = 0.812), lowest oxygen saturation (p = 0.0001, r = 0.540) and time of sleep spent with blood oxygen saturation less than 90% (p = 0.0001, r = 0.485). The most commonly reported complications were throat dryness (11 patients) and minor difficulties in swallowing (5 patients transient, 3 patients constant). We conclude that a PDPFEx is a promising new surgical method; however, further controlled studies are needed to demonstrate its safety and efficacy for OSAS treatment in adults.

scholarly journals Analysis of Metabolites Changes on Obstructive Sleep Apnea Patients After Multilevel Sleep Surgery

2020 ◽  
Author(s):  
Abdulmohsen Alterki ◽  
Shibu Joseph ◽  
Thangavel Alphonse Thanaraj ◽  
Irina Al-Khairi ◽  
Preethi Cherian ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Metabolic Status ◽  
Apnea Hypopnea Index ◽  
P Value ◽  
Upper Airways ◽  
Sleep Surgery ◽  
Post Surgery ◽  
Obstructive Sleep ◽  
Increased Risk

Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. Methods: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and 5 months after surgery. Results: The mean Apnea Hypopnea Index (AHI) significantly dropped from 22.0 &plusmn; 18.5 events/hour to 8.97 &plusmn; 9.57 events/hour (p-Value &lt;0.001). The Epworth&rsquo;s sleepiness Score (ESS) dropped from 12.8 &plusmn; 6.23 to 2.95 &plusmn; 2.40 (p-Value &lt;0.001) indicating success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value&lt;0.05) whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value&lt;0.05) after surgery. Conclusion: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in improvement in metabolic status that was characterized by decreased TG, PCs and Cer metabolites post-surgery indicating that the success of the surgery positively impacted the metabolic status of these patients.

Sign in / Sign up

Export Citation Format

Share Document