scholarly journals Urine 5-Eicosatetraenoic Acids as Diagnostic Markers for Obstructive Sleep Apnea

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1242
Author(s):  
Hyun-Woo Shin ◽  
Kumsun Cho ◽  
Chae-Seo Rhee ◽  
Il-Hee Hong ◽  
Seok Hyun Cho ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Mononuclear Cells ◽  
Hypoxia Inducible Factor ◽  
Apnea Hypopnea Index ◽  
Hypoxia Inducible Factor 1 ◽  
Human Mononuclear Cells ◽  
Obstructive Sleep ◽  
Arachidonic Acid Derivatives

Early detection of obstructive sleep apnea (OSA) is needed to reduce cardiovascular sequelae and mortality. Full-night polysomnography has been used for diagnosing OSA, but it is too expensive and inconvenient for patients to handle. Metabolome-wide analyses were performed to find and validate surrogate markers for OSA. We further investigated the mechanism underlying hypoxic induction of the markers in human cells and mice. Arachidonic acid derivatives 5-HETE and 5-oxoETE were detected in urine samples. The levels (mean ± SD, ng per mg creatinine) of 5-HETE and 5-oxoETE were 56.4 ± 26.2 and 46.9 ± 18.4 in OSA patients, respectively, which were significantly higher than those in controls (22.5 ± 4.6 and 18.7 ± 3.6). Both levels correlated with the apnea-hypopnea index and the lowest oxygen saturation on polysomnography. After the treatment with the continuous positive airway pressure, the metabolite levels were significantly reduced compared with those before the treatment. In human mononuclear cells subjected to intermittent hypoxia, 5-HETE and 5-oxoETE productions were induced by hypoxia-inducible factor 1 and glutathione peroxidase. When mice were exposed to intermittent hypoxia, 5-HETE and 5-oxoETE were excreted more in urine. They were identified and verified as new OSA markers reflecting hypoxic stress. The OSA markers could be used for OSA diagnosis and therapeutic evaluation.

scholarly journals High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea

2021 ◽  
Vol 10 (7) ◽  
pp. 1387
Author(s):  
Raphael Boneberg ◽  
Anita Pardun ◽  
Lena Hannemann ◽  
Olaf Hildebrandt ◽  
Ulrich Koehler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Vascular Risk Factor ◽  
High Plasma ◽  
Apnea Hypopnea Index ◽  
Hypoxic Stress ◽  
Peripheral Blood Mononuclear ◽  
Obstructive Sleep

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.

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 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 miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

2020 ◽  
Vol 21 (3) ◽  
pp. 999
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Mao-Chang Su ◽  
Chien-Hung Chin ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Target Genes ◽  
Apnea Hypopnea Index ◽  
Gene Expressions ◽  
Obstructive Sleep ◽  
Tnf Α

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes—including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4—were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

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&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.

scholarly journals Association Of Nocturnal Intermittent Hypoxia With Heat Shock Protein 70 In Patients With Obstructive Sleep Apnea: A Pilot Study

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Irina M. Madaeva ◽  
Nadezhda A. Kurashova ◽  
Natalya V. Semenova ◽  
Lubov I. Kolesnikova ◽  
Sergei I. Kolesnikov
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Intermittent Hypoxia ◽  
Control Group ◽  
Apnea Hypopnea Index ◽  
Hsp70 Level ◽  
Obstructive Sleep

Introduction — Nocturnal intermittent hypoxia in obstructive sleep apnea (OSA) causes cellular stress and consequent change in inducible heat shock protein 70 (HSP70) level. Thus, the objective of this study was to determine the relationship among nocturnal hypoxia and the serum HSP70 level in patients with severe OSA. Material and Methods — The study involved 34 patients with a clinical diagnosis of moderate to severe OSA (24 men and 10 women). Patients without OSA (10 men and 5 women) were included as a control group. The groups were similar in age. The polysomnographic monitoring was carried by standart methodology. Blood sampling for determining the HSP70 level was carried out between 8:00 and 9:00 am after polysomnographic monitoring. Results — The results of this study demonstrated a high apnea/hypopnea index (AHI), which determined the OSA severity and decreased the blood oxygen saturation (SaO2) (p<0.05). Sleep fragmentation in OSA patients confirmed an increase in respiratory arousal index (ArI). The HSP70 level significantly increased in OSA patients compared with the control group. Correlation analysis showed a positive relationship between HSP70 and AHI (R=0.5) in patients with OSAS, as well as a negative relationship between HSP70 and SaO2 (R=-0.3). Conclusion — Our results demonstrated a high level of HSP70 in patients with severe OSA syndrome vs. those without it. In OSA patients, a direct correlation was found between the HSP70 level and AHI, as well as an inverse correlation between the AHI level and SaO2. These findings suggested an association between the level of inducible HSP70 and nocturnal hypoxia in OSA patients.

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