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Obstructive sleep apnoea syndrome – an oxidative stress disorder
Abstract
Obstructive sleep apnoea syndrome (OSA) is associated with increased cardiovascular morbidity and mortality. However, the underlying mechanisms are not entirely understood. This review will summarize the evidence that substantiates the notion that the repeated apnoea-related hypoxic events in OSA, similarly to hypoxia/reperfusion injury, initiate oxidative stress. Thus, affecting energy metabolism, redox-sensitive gene expression, and expression of adhesion molecules. A limited number of studies substantiate this hypothesis directly by demonstrating increased free radical production in OSA leukocytes and increased plasma-lipid peroxidation. A great number of studies, however, support this hypothesis indirectly. Increase in circulating levels of adenosine and urinary uric acid in OSA are implicated with increased production of reactive oxygen species (ROS). Activation of redox-sensitive gene expression is suggested by the increase in some protein products of these genes, including VEGF, erythropoietin, endothelin-1, inflammatory cytokines and adhesion molecules. These implicate the participation of redox-sensitive transcription factors as HIF-1 AP-1 and NFkappaB. Finally, adhesion molecule-dependent increased avidity of OSA monocytes to endothelial cells, combined with diminished NO bioavailability, lead to exaggerated endothelial cell damage and dysfunction. Cumulatively, these processes may exacerbate atherogenic sequelae in OSA.
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“Long-term chronic hypoxia caused by OSA can lead to several physiological and biochemical modifications, such as changes in the NLR, PLR, and levels of C-reactive proteins and markers of serum inflammation [33–37].”
From Airway morphology, hyoid position, and serum inflammatory markers of obstructive sleep apnea in children treated with modified twin-block appliances (2025) · cites this paper as [33]
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Oxidative Stress in Obstructive Sleep Apnea Syndrome: Putative Pathways to Hearing System Impairment
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BackgroundInfluentialSelf-citationObstructive sleep apnea, gestational hypertension and preeclampsia
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InfluentialThe Role of Vitamin C in Two Distinct Physiological States: Physical Activity and Sleep
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“OSA, present in approximately 3% to 7% of the general population,(6) is associated with oxidative stress, vascular endothelium damage, and dysfunction.(7,8) There are only 2 case reports of OSA in FRDA,(9,10) while another study reported decreased REM time and latency.”
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InfluentialObstructive Sleep Apnea in Neuro-Ophthalmology
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“The reduced ability of the optic nerve microcirculation to autoregulate during these periods in OSA is believed to result from an imbalance between nitric oxide and endothelin (79,95,96).”
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“OSA is well-known to elicit systemic inflammation in males [30–32], the markers of which correlate with cardiovascular disease in both OSA and non-OSA cohorts [30,32].”
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“Oxidative stress plays an important role in various diseases as well as in OSA, which causes an effect similar to ischemia-reperfusion [18] in which there is activation of xanthine oxidase, leading to the formation free radicals and further imbalance between oxidants and antioxidants [4-6].”
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Conotte, S., Tassin, A., Conotte, R., Colet, J., Boudjeltia, K. Z., & Legrand, A. (2018) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2018.02.015 · Cited by 24
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Endothelin-1 Gene Variant Lys198Asn and Plasma Endothelin Level in Obstructive Sleep Apnea
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“] examined the functional relationship between this polymorphism and plasma EDN1 levels. This study disclosed that among pregnant women, the T allele carrier status is correlated with higher levels of both blood pressure at rest and plasma EDN1 after correction for body mass index (BMI).With regard to EDN1 plasma leve…”
ResultWu, K., Lin, C.-C., Chiu, C., & Liaw, S. (2009) · CHEST Journal · doi:10.1378/chest.09-0936 · Cited by 24
Resting energy expenditure in OSAS: the impact of a single CPAP application
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“SAS has been termed an “oxidative stress disorder” in a classical review [12].”
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Factors influencing sleep time with oxygen saturation below 90% in sleep‐disordered breathing
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“Regardless of underlying etiology, episodic collapse of the upper airway leads to chronic intermittent hypoxia (CIH), a hallmark of OSA, which triggers oxidative stress and chronic inflammation.(15,16) Consequently, all these pathophysiological processes give rise to detrimental effects on cardiovascular, neurocogniti…”
BackgroundAntioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial
Wu, K., Su, X., Li, G., & Zhang, N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148519 · Cited by 23
“Some studies have even reported that OSAS is an oxidative stress disease [8].”
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“This could be linked to higher oxidative stress [25-27], endothelial dysfunction [28-30], less nitric oxide production [31], and inflammation [32].”
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“…apnea), repeated cycles of hypoxia– re-oxygenation increase ROS production, and thereby lead to maladaptive changes in respiratory and cardiovascular system function, metabolism and redox-sensitive gene expression (Lavie, 2003; Neubauer, 2001; Prabhakar et al., 2007; Semenza and Prabhakar, 2007).”
BackgroundObstructive sleep apnoea syndrome promotes reversal albuminuria during sleep
Daskalopoulou, E., Liavvas, C. H., Nakas, C. T., Vlachogiannis, E., Bouros, D. E., & Dombros, N. (2010) · Sleep And Breathing · doi:10.1007/s11325-010-0408-6 · Cited by 23
“Treatment of OSAS with continuous positive airway pressure (CPAP) has been found to reduce the sympathetic nervous activity, the oxidative stress, the inflammatory and atherosclerosis provoking factors [ 3 ], the levels of systemic blood pressure, especially in hypertensives [9], reducing significantly the morbidity a…”
BackgroundTumor Necrosis Factor-α Expression in Uvular Tissues Differs Between Snorers and Apneic Patients
Loubaki, L., Jacques, É., Semlali, A., Biardel, S., Chakir, J., & Sériès, F. (2008) · CHEST Journal · doi:10.1378/chest.08-0886 · Cited by 23
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NADPH oxidase p22phox polymorphisms and oxidative stress in patients with obstructive sleep apnoea
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Clinical Perspective of Obstructive Sleep Apnea–Induced Cardiovascular Complications
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“These oxidant species can activate redox-sensitive signaling pathways that initiate adaptive responses to hypoxia (such as hypoxia inducible factor 1 (cid:1) ) (57) and inflammatory pathways (65).”
InfluentialTóthová, Ľ., Hodosy, J., Mucska, I., & Celec, P. (2013) · Sleep And Breathing · doi:10.1007/s11325-013-0919-z · Cited by 23
Sleep disordered breathing in chronic heart failure
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“These include recurrent hypoxemia and re-oxygenation stress [66, 67], hypercapnia, intrathoracic pressure changes, frequent arousals [68], endothelial dysfunction [69, 70], inflammation [71], a hypercoagulable state [72, 73] and metabolic dysregulation [74, 75].”
BackgroundUrinary F2-isoprostane metabolite levels in children with sleep-disordered breathing
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“Oxidant stress-related mechanisms were proposed as a major contributor to cardiovascular morbidity in adult patients with sleep-disordered breathing (SDB) [1, 2], and there is evidence of their improvement after continuous positive airway pressure (CPAP) treatment [3–6].”
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“This suppresses both the rate of transcription of the eNOS gene and the stability of transcribed mRNA.(1,4) Repetitive nocturnal hypoxemia and reoxygenation in OSAS also increase generation of superoxide and other reactive oxygen species.”
BackgroundInfluentialÖzol, D., Türkay, C., Kasapoğlu, B., Karamanlı, H., & Yıldırım, Z. (2010) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2010.0033 · Cited by 22
Changes in serum levels of MDA and MMP-9 after UPF in patients with OSAS
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“oxidative stress either stemming from excessive ROS production because of a direct exposure to trauma or other triggering factors may lead to increased CVD morbidity in OSAS [14].”
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“[7,8] The patient complains of loud snoring, stoppage of breathing, daytime somnolence, and excessive chronic fatigue.”
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Sleep-Disordered Breathing in Pregnancy
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Circulating Carbon Monoxide Level Is Elevated After Sleep in Patients With Obstructive Sleep Apnea
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“OSA is accompanied by local and systemic inflammation [2, 3].”
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“While the underlying mechanisms are not entirely understood, release of pro-inflammatory factors and increased oxidative stress are commonly cited (18).”
BackgroundHydroxyurea treatment effect on children with sickle cell disease and obstructive sleep apnea
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Sleep apnoea is common in severe peripheral arterial disease
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Obstructive sleep apnea—an overview of the disorder and its consequences
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Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta‐analysis
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“Patients with OSA undergo repeated episodes of hypoxia, and the reoxygenation ⁄ reperfusion phase is believed to result in ROS (reactive oxygen species) production and oxidative stress (Lavie, 2003; Suzuki et al., 2006).”
BackgroundDünnwald, T., Bernardi, L., Gordin, D., Sandelin, A., Syreeni, A., Fogarty, C. L., Kytö, J., Gatterer, H., Lehto, M. J., Hörkkö, S., et al. (2013) · Diabetes · doi:10.2337/db13-0167 · Cited by 19
“OSAS is actually characterized by very short exposures to hypoxia (approximately 30 s) that arise many times (hundreds) during nighttime, leading to a stress response because of lack of time for a compensatory effect (40).”
BackgroundLin, C.-C., Liaw, S., Chiu, C., Chen, W.-J., Lin, M.-W., & Chang, F.-T. (2016) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2016.03.001 · Cited by 19
Effect of Uvulopalatopharyngoplasty on Leptin and Endothelial Function in Sleep Apnea
Lin, C.-C., Wang, Y., Lee, K., Liaw, S., & Chiu, C. (2014) · Annals of Otology Rhinology & Laryngology · doi:10.1177/0003489414521385 · Cited by 19
“Annals of Otology, Rhinology & Laryngology 123(1):40-46.”
Yang, C.-H., Zhuang, W.-L., Shen, Y.-J., Lai, C. J., & Kou, Y. R. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00166 · Cited by 19
“Indeed, in these patients, repetitive periods of upper airway collapse result in cyclic periods of hypoxia/re-oxygenation (Lavie, 2003), which seems to produce excess ROS in the airways (Prabhakar, 2001).”
BackgroundSleep Disordered Breathing During Live High-Train Low in Normobaric Versus Hypobaric Hypoxia
SAUGY, J. J., Schmitt, L., Fallet, S., Faiss, R., Vésin, J.-M., Bertschi, M., Heinzer, R. C., & Millet, G. P. (2016) · High Altitude Medicine & Biology · doi:10.1089/ham.2016.0049 · Cited by 19
“This episodic breathing observed in HH might lead to intermittent hypoxia and, consequently, have clinical consequences: the desaturation–reoxygenation sequence is a typical pattern coupled with the majority of respiratory events defining intermittent hypoxia leading to oxidative stress with production of reactive oxyg…”
InfluentialZhou, X., Tang, S., Hu, K., Zhang, Z., Liu, P., Luo, Y., Kang, J., & Xu, L. (2018) · Sleep And Breathing · doi:10.1007/s11325-018-1656-0 · Cited by 19
Okuda, N., Ito, T., Emura, N., Suwa, M., Hayashi, T., Yoneda, H., & Kitaura, Y. (2007) · CHEST Journal · doi:10.1378/chest.06-2444 · Cited by 19
Effect of adenotonsillectomy on the use of respiratory medication
Piessens, P., Hens, G., Lemkens, N., Schrooten, W., Debruyne, F., & Lemkens, P. (2012) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2012.02.069 · Cited by 19
“The intermittent upper airway obstruction in obstructive sleep apnoea syndrome and the resulting alveolar hypoxia lead to the release of oxygen free radicals and cysteinyl leukotrienes in the airways [15].”
BackgroundFitzgibbons, C., Goldstein, R. L., Gottlieb, D. J., & Moy, M. L. (2019) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7874 · Cited by 20
OBSTRUCTIVE SLEEP APNEA AND INSULIN RESISTANCE: A ROLE FOR MICROCIRCULATION?
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Day, R. M., Matus, I., Suzuki, Y., Yeum, K., Jian, Q. I. N., Park, A.-M., Jain, V., Kuru, T., & Tang, G. (2009) · Respirology · doi:10.1111/j.1440-1843.2009.01623.x · Cited by 18
Moradi, S., Mohammadi, H., Javaheri, A., Ghavami, A., & Rouhani, M. H. (2019) · Hormone and Metabolic Research · doi:10.1055/a-0957-3256 · Cited by 18
“OSA can affect blood pressure by stimulating aldosterone secretion and promoting accumulation of fluid in the neck [68, 69] .”
BackgroundWang, F., Liu, Y., Xu, H., Qian, Y., Zou, J., Yi, H., Guan, J., & Yin, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-56601-w · Cited by 18
Keleş, T., Durmaz, T., Bayram, N., Çiftçi, B., Yeter, E., Akçay, M., & Bozkurt, E. (2009) · Echocardiography · doi:10.1111/j.1540-8175.2009.00957.x · Cited by 18
Bhadriraju, S., Kemp, C., Cheruvu, M., & Bhadriraju, S. (2008) · Critical Pathways in Cardiology A Journal of Evidence-Based Medicine · doi:10.1097/hpc.0b013e31818ae644 · Cited by 19
Chuang, L., Chen, N., Lin, S., Chang, Y., Liao, H.-R., Lin, Y., Chao, I.-J., Lin, Y., & Pang, J. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113304 · Cited by 18
“Growing evidence points out the importance of oxidative stress and activated inflammatory cells that play a role in the association between OSA and cardiovascular morbidity [40].”
BackgroundArrhythmia and sleep-disordered breathing in patients undergoing cardiac surgery
Unosawa, S., Sezai, A., Akahoshi, T., Niino, T., Shimura, K., Shiono, M., Sekino, H., & Akashiba, T. (2012) · Journal of Cardiology · doi:10.1016/j.jjcc.2012.01.012 · Cited by 18
“[5] Lavie L.”
BackgroundTuleta, I., Pabst, S., Juergens, U. R., Nickenig, G., & Skowasch, D. (2011) · The EPMA Journal · doi:10.1007/s13167-011-0070-5 · Cited by 19
“[86], partly as a consequence of the overexpression of asymmetric dimethylarginine (ADMA) - endogenous inhibitor of NO production [87] observed in OSA.”
BackgroundNocturnal change of circulating intercellular adhesion molecule 1 levels in children with snoring
Kaditis, A. G., Alexopoulos, E. Ι., Kalampouka, E., Hatzi, F., Καραδόντα, Ι., Kyropoulos, T., Kaditis, D. G., Gourgoulianis, K. I., & Syrogiannopoulos, G. A. (2007) · Sleep And Breathing · doi:10.1007/s11325-007-0117-y · Cited by 18
“Because nocturnal intermittent hypoxemia related to sleep apnea can induce expression of ICAM-1 in endothelial cells [4], we hypothesized that measuring the overnight change in cICAM-1 would be a more sensitive method to detect endothelial activation than using only one concentration measurement.”
BackgroundMethodInfluentialEvidence of hypoxic tolerance in weak upper airway muscle from young mdx mice
Burns, D. P., & O’Halloran, K. D. (2015) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2015.12.001 · Cited by 17
“It is well documented that hypoxia is a driver of inflammation (Lavie, 2012) and oxidative stress (Lavie, 2003).”
BackgroundIntermittent hypoxia treatments cause cellular priming in human microglia
Felice, M. D., Germelli, L., Piccarducci, R., Pozzo, E. D., Giacomelli, C., Baccaglini‐Frank, A., & Martini, C. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17682 · Cited by 16
Tan, T., Liou, C., Friedman, M., Lin, H., Chang, H., & Lin, M. (2012) · The Neurologist · doi:10.1097/nrl.0b013e3182675344 · Cited by 17
“This desaturation/ reoxygenation cycle is probably a source of oxidative stress with production of reactive oxygen species.(19) The increased levels of reactive oxygen species finally contribute to produce systemic inflammation.”
BackgroundIntermittent hypoxia reduces cerebrovascular sensitivity to isocapnic hypoxia in humans
Querido, J. S., Godwin, J., & Sheel, A. W. (2007) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2007.11.002 · Cited by 17
Sleep Disorders and Home Dialysis
Hanly, P. J. (2009) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2009.02.004 · Cited by 17
Gao, J., Cao, H., Zhang, Q., & Wang, B. (2020) · Sleep And Breathing · doi:10.1007/s11325-020-02204-z · Cited by 18
Baldwin, C. M., Bell, I. R., Guerra, S., & Quan, S. F. (2005) · Sleep And Breathing · doi:10.1007/s11325-005-0025-y · Cited by 17
“Mechanisms implicated in mediating the increase risk of CVD in OSA include enhanced free radical activity [19].”
BackgroundVascular endothelial dysfunction in patients with mild Obstructive Sleep Apnea Syndrome
Duchna, H. W., Stoohs, R. A., Guilleminault, C., Anspach, M. C., Schultze‐Werninghaus, G., & Orth, M. (2006) · Wiener Medizinische Wochenschrift · doi:10.1007/s10354-006-0341-2 · Cited by 17
“Thus, OSAS is called an “oxidative stress disorder”, for elevated levels of reactive oxygen species (ROS) have been shown in OSAS-patients as a result from repetitive oxygen desaturation and reoxygenation [38].”
BackgroundMorrell, M. J. (2004) · SLEEP · doi:10.1093/sleep/27.2.186 · Cited by 17
Tong, X., Yang, L., Jiang, C., Weng, Z., Zu, A., Hou, Y., Fang, Y., Yang, W., & Sun, S. (2023) · Reproductive Sciences · doi:10.1007/s43032-022-00904-3 · Cited by 16
“In addition, cyclic reoxygenation after IH also promotes the production of reactive oxygen species (ROS) in OSA [50].”
BackgroundInfluentialKarandikar, K., Le, T., Sa-ngasoongsong, A., Wongdhamma, W., & Bukkapatnam, S. (2013) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2013.6611191 · Cited by 16
“Several OSA detection approaches based on correlating the statistical patterns of heart rate, respiration rate, and oxygen saturation (SpO2) signals during OSA episodes have been reported [2-4].”
BackgroundObstructive sleep apnea and endothelial progenitor cells
Feng, J., Qing, W. A. N. G., Wu, Q., & Xin, S. U. N. (2013) · Patient Preference and Adherence · doi:10.2147/ppa.s51562 · Cited by 17
“In turn, increased oxidative stress will lead to activation of nuclear factor (NF)-κB, and hence increased expression of a number of downstream NF-κB target genes; for example, proinflammatory cytokines, such as TNF-α, IL-6, and IL-8, as well as adhesion molecules such as intercellular adhesion molecule 1.(57)”
Metadata
- Authors
- Lavie, L.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Lavie, Lena
- Venue
- Sleep Medicine Reviews
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 7
- Issue
- 1
- Pages
- 35-51
- ISSN
- 1087-0792 (ISSN-L)
- OpenAlex
- W1988114644
- Cited by
- 993
- References
- 134
- Citations by year
- 2026: 17 · 2025: 44 · 2024: 28 · 2023: 30 · 2022: 33 · 2021: 43 · 2020: 42 · 2019: 31 · 2018: 38 · 2017: 37 · 2016: 44 · 2015: 51 · 2014: 58 · 2013: 48 · 2012: 51
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Sleep Medicine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, State of Israel
- Topics
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- obstructive sleep apnea, oxidative stress, hypoxia/reoxygenation injury, reactive oxygen species, lipoprotein oxidation, adhesion molecules, adenosine, uric acid, HIF-1, NF-κB, AP-1, endothelial dysfunction, monocyte adhesion, nitric oxide bioavailability, atherosclerosis, cardiovascular risk
- MeSH terms
- Cardiovascular Diseases, Free Radicals, Humans, Leukocytes, Lymphokines, Nitric Oxide, Lipid Peroxidation, Endothelial Growth Factors, Oxidative Stress, Hyperhomocysteinemia, Sleep Apnea, Obstructive, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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