scholarly journals Alternations of Circadian Clock Genes Expression and Oscillation in Obstructive Sleep Apnea

2019 ◽  
Vol 8 (10) ◽  
pp. 1634 ◽  
Author(s):  
Yang ◽  
Lin ◽  
Lin ◽  
Lin ◽  
Chen ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Clock Genes ◽  
Expression Patterns ◽  
Binary Logistic Regression Analysis ◽  
Chain Reactions ◽  
Obstructive Sleep ◽  
Circadian Clock Genes ◽  
Normal Controls

Circadian misalignment plays an important role in disease processes and can affect disease severity, treatment outcomes, and even survivorship. In this study, we aim to investigate whether expression and daily oscillation patterns of core circadian clock genes were disturbed in patients with obstructive sleep apnea/hypopnea (OSA) syndrome. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes in leukocytes of peripheral blood collected at 12 AM, 6 AM, 12 PM, and 6 PM from 133 patients with OSA and 11 normal controls. Daily expression patterns of the nine circadian clock genes were observed in normal controls, but three of these genes (BMAL1, CLOCK, CRY2) were disrupted in patients with OSA. The expressions of eight circadian clock genes (except PER1) at midnight were significantly downregulated in patients with severe OSA. Binary logistic regression analysis selected CRY1 and PER3 as independent factors for severe OSA and showed that the combined expressions of CRY1 and PER3 enhanced the capability of predicting severe OSA (Odds ratio, 5.800; 95% CI, 1.978 to 17.004; p = 0.001). Our results show that combined expressions of CRY1 and PER3 at midnight could be a potential predictor for severe OSA.

scholarly journals The rat cerebral vasculature exhibits time-of-day-dependent oscillations in circadian clock genes and vascular function that are attenuated following obstructive sleep apnea

2016 ◽  
Vol 37 (8) ◽  
pp. 2806-2819 ◽  
Author(s):  
David J Durgan ◽  
Randy F Crossland ◽  
Robert M Bryan
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Circadian Clock ◽  
Diurnal Rhythm ◽  
Vascular Function ◽  
Clock Genes ◽  
Cerebral Arteries ◽  
Active Phase ◽  
Time Of Day ◽  
Obstructive Sleep

Circadian clock components oscillate in cells of the cardiovascular system. Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function. Apneas were produced in rats during sleep. Following two weeks of sham or obstructive sleep apnea, cerebral arteries were isolated over 24 h for mRNA and functional analysis. mRNA expression of clock genes exhibited 24-h rhythms in cerebral arteries of sham rats (p < 0.05). Interestingly, peak expression of clock genes was significantly lower following obstructive sleep apnea (p < 0.05). Obstructive sleep apnea did not alter clock genes in the heart, or rhythms in locomotor activity. Isolated posterior cerebral arteries from sham rats exhibited a diurnal rhythm in sensitivity to luminally applied ATP, being most responsive at the beginning of the active phase (p < 0.05). This rhythm was absent in arteries from obstructive sleep apnea rats (p < 0.05). Rhythms in ATP sensitivity in sham vessels were absent, and not different from obstructive sleep apnea, following treatment with L-NAME and indomethacin. We conclude that cerebral arteries possess a functional circadian clock and exhibit a diurnal rhythm in vasoreactivity to ATP. Obstructive sleep apnea attenuates these rhythms in cerebral arteries, potentially contributing to obstructive sleep apnea-associated cerebrovascular disease.

scholarly journals Cone-beam CT analysis of patients with obstructive sleep apnea compared to normal controls

2016 ◽  
Vol 46 (1) ◽  
pp. 9 ◽  
Author(s):  
Allison Buchanan ◽  
Ruben Cohen ◽  
Stephen Looney ◽  
Sajitha Kalathingal ◽  
Scott De Rossi
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cone Beam Ct ◽  
Cone Beam ◽  
Obstructive Sleep ◽  
Ct Analysis ◽  
Normal Controls

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 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.

Abolished Daily Expression Patterns of SIRT1, SIRT2, and SIRT5 in Human Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4613-4613
Author(s):  
Ming-Yu Yang ◽  
Pai-Mei Lin ◽  
Jui-Feng Hsu ◽  
Wen-Chi Yang ◽  
Yi-Chang Liu ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Myeloid Leukemia ◽  
Clock Genes ◽  
Expression Patterns ◽  
Healthy Individuals ◽  
Daily Pattern ◽  
Genes Expression ◽  
Circadian Clock Genes

Abstract Abstract 4613 Circadian rhythms regulate various functions of human body and disruption of circadian rhythm has been associated with cancer development and tumor progression. Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Many transcriptional regulators are histone acetyltransferases (HAT) or histone deacetylases (HDAC). As clock function and integration of inputs rely on transcriptional regulation, it is possible that chromatin is remodeled during circadian cycles and in response to signals that regulate the clock. SIRT1 (sirtuin 1) is a HDAC that has recently been identified as a crucial modulator of the circadian clock machinery. To date, at least 7 SIRT genes (SIRT1–7) have been identified. In our previous report we have demonstrated the daily expression patterns of PER1, PER2, PER3, CRY1, CRY2, and CKIe in peripheral blood (PB) of healthy individuals were abolished in chronic myeloid leukemia (CML) patients and partial recoveries of daily patterns were observed in CML patients with complete cytogenetic response (CCyR) and major molecular response (MMR) post-imatinib treatment [J Biol Rhythms 2011]. In this study we further investigated the expression profiles of the 7 SIRT genes (SIRT1–7) in PB total leukocytes from 49 CML and 22 healthy volunteers. Collection of PB was carried out at four time points: 2000 h, 0200 h, 0800 h, and 1400 h, respectively. In PB total leukocytes of healthy individuals, the daily pattern of SIRT1 (p < 0.01) and SIRT5 (p < 0.05) expression level peaked at 0200 h, and SIRT2 (p < 0.01) peaked at 0800 h. Daily pattern expression of these 3 genes was abolished in newly diagnosed pre-imatinib mesylate treated and blast crisis-phase CML patients. Partial daily patterns of gene expression recoveries were observed in CML patients with CCyR and MMR. In some serial monitored individual patients, the recoveries of oscillations of SIRT1, 2, and 5 genes expression accompanied with the disappearance of BCR-ABL transcripts were also noted. The expression of SIRT3, 6, and 7 did not show a time-dependent variation among the healthy and CML patients. SIRT4 expression was undetectable both in the healthy and CML patients. Updated in vitro study results of the regulation of SIRT1, 2, and 5 genes on circadian clock genes expression will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Digital fluoroscopy before and after laser uvulopalatopharyngoplasty in obstructive sleep apnea

1997 ◽  
Vol 38 (2) ◽  
pp. 214-221 ◽  
Author(s):  
Y. Tsushima ◽  
J. Antila ◽  
E. Laurikainen ◽  
E. Svedström ◽  
O. Polo ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Poor Responders ◽  
Dynamic Changes ◽  
Digital Fluoroscopy ◽  
Obstructive Sleep ◽  
Before And After ◽  
Cephalometric Measurements ◽  
Normal Controls

Purpose: to study the changes in pharyngeal behavior after laser uvulopalatopharyngoplasty (LUPPP). Material and Methods: the dynamic changes in the upper airway size were evaluated with digital fluoroscopy in 24 patients with obstructive sleep apnea (OSA) before and after LUPPP and in 16 normal controls, while they were awake and breathing normally. Cephalometric measurements were also made. the patients were classified into the categories of good and poor responders by means of a static-charge-sensitive bed. Results: Following LUPPP, collapsibility at the velopharyngeal level was within the normal range in 15 of 17 good responders, but only in 2 of 7 poor responders (p=0.0086). the minimum airway size at the same level showed a similar trend. in 3 of 7 poor responders the hyoid bone was positioned more caudally than in the good responders (p=0.017). Conclusion: Digital fluoroscopy provides information on the change in upper airway behavior after LUPPP.

scholarly journals The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer

2020 ◽  
Vol 21 (6) ◽  
pp. 444-453
Author(s):  
Anna Brzecka ◽  
Karolina Sarul ◽  
Tomasz Dyła ◽  
Marco Avila-Rodriguez ◽  
Ricardo Cabezas-Perez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sleep Disorders ◽  
Intermittent Hypoxia ◽  
Clock Genes ◽  
Cell Cancer ◽  
Cancer Risk Factors ◽  
Obstructive Sleep ◽  
Increased Risk

Background: Sleep disorders have emerged as potential cancer risk factors. Objective: This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer. Results: Sleep disorders result in abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which is frequently experienced by obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation. Discussion: During short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer was observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated. Conclusion: Several factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions.

scholarly journals Obstructive sleep apnea in children aged 3 years and younger: Rate and risk factors

2019 ◽  
Vol 25 (7) ◽  
pp. 432-438
Author(s):  
Sarah Selvadurai ◽  
Giorge Voutsas ◽  
Evan J Propst ◽  
Nikolaus E Wolter ◽  
Indra Narang
Keyword(s):  
Risk Factors ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nasal Congestion ◽  
Retrospective Chart Review ◽  
Binary Logistic Regression ◽  
High Rate ◽  
Binary Logistic Regression Analysis ◽  
Healthy Children ◽  
Obstructive Sleep

Abstract Objective Undiagnosed and untreated obstructive sleep apnea (OSA) can predispose children to neurobehavioural consequences. However, there is a lack of data identifying rate of, and risk factors for, OSA in very young healthy children. The objective of this study was to determine the rate of OSA and identify risk factors associated with the presence and severity of OSA in children aged 3 years and younger. Methods This was a retrospective chart review of healthy children between 1 and 3 years old who had a baseline polysomnogram (PSG) between January 2012 and June 2017. Patient demographics, referral history, and PSG data were recorded. Results One hundred and thirteen children were referred for a PSG, of which 66 (58%) were diagnosed with OSA and 47 (42%) did not have OSA. In the OSA group, 13 (20%) were mild and 53 (80%) were moderate-severe. Nasal congestion (P=0.001), adenoid hypertrophy (P=&lt;0.001), and tonsillar hypertrophy (P=0.04) reported at the time of referral were more common in the OSA group compared to the no-OSA group. Binary logistic regression analysis showed that referral from an otolaryngologist (odds ratio=2.6, 95% confidence interval=1.1 to 6.0) were associated with moderate-severe OSA. Conclusion A high rate of OSA was found among children aged 3 years and younger. Children referred by an otolaryngologist are more likely to be diagnosed with moderate-severe OSA. Children aged 3 years and younger with symptoms of OSA should be considered high-risk for OSA and be prioritized for early PSG and management.

Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5

2021 ◽  
Author(s):  
Jing Zhang ◽  
Lijia Zhao ◽  
Yating Li ◽  
Hao Dong ◽  
Haisen Zhang ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Expression Patterns ◽  
Current Data ◽  
Orphan Receptor ◽  
Luciferase Reporter ◽  
Mobility Shift ◽  
Rhythmic Expression ◽  
Clock System ◽  
Circadian Clock Genes

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

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