Cited by 993Obstructive Sleep Apnea ResearchNitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative Stress

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Obstructive sleep apnoea syndrome – an oxidative stress disorder

Lavie, Lena·2003·Sleep Medicine Reviews

DOI 10.1053/smrv.2002.0261

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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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Lipid peroxidation and DNA damage in apnea patients with or without metabolic syndrome
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Fibrinolytic Activity and Platelet Function in Subjects with Obstructive Sleep Apnoea and a Patent Foramen Ovale: Is There an Option for Prevention of Ischaemic Stroke?
Reggiani, M., Karttunen, V., Wartiovaara‐Kautto, U., Riutta, A., Uchiyama, S., & Hillbom, M. (2012) · Stroke Research and Treatment · doi:10.1155/2012/945849 · Cited by 6
“Hypoxia has been postulated as inducing increased production of reactive oxygen species and adhesion molecules in leukocytes and the endothelium and decreased NO availability, leading to endothelial dysfunction [36].”
Background
Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study
Ahiawodzi, P. D., Kerber, R. A., Taylor, K. C., Groves, F. D., O’Brien, E. A., Ix, J. H., Kizer, J. R., Djoussé, L., Tracy, R. P., Newman, A. B., et al. (2017) · Biomarkers · doi:10.1080/1354750x.2016.1276966 · Cited by 6
“In sleep-disordered breathing, episodes of hypoxia occur repeatedly, which impair production of adenosine triphosphate (ATP), up-regulate glycolysis and, consequently, produce reactive oxygen species (ROS) (Lavie 2003, Zhang and Veasey 2012).”
Background
Assessment of oxidative stress markers and hearing thresholds in patients with obstructive sleep apnea-hypopnoea treated with cysteine and superoxide dismutase therapy.
Serra, A., Maiolino, L., Cocuzza, S. G., Luca, M. D., Campione, G., Licciardello, L., & Mauro, P. D. (2016) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 6
Electrocardiographic variables in children with syndromic craniosynostosis and primary snoring to mild obstructive sleep apnea: significance of identifying respiratory arrhythmia during sleep
Kakar, E., Corel, L. J. A., Tasker, R. C., de Goederen, R., Wolvius, E. B., Mathijssen, I. M. J., & Joosten, K. F. M. (2017) · Sleep Medicine · doi:10.1016/j.sleep.2017.09.036 · Cited by 6
Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia
Moya, E. A., Arias, P., & Iturriaga, R. (2018) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155418776229 · Cited by 6
The Frequency of Monocyte Chemoattractant Protein-1 Gene Polymorphism in Obstructive Sleep Apnea Syndrome
Kerget, B., Araz, Ö., Erdem, H. B., & Akgün, M. (2019) · Lung · doi:10.1007/s00408-019-00256-x · Cited by 6
Non-linear HRV Analysis to Quantify the Effects of Intermittent Hypoxia Using an OSA Rat Model
Romero, D., & Jané, R. (2019) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2019.8857636 · Cited by 6
“However, it has been reported that an elevated sympathetic tone of the autonomic nervous system (ANS) [4], oxidative stress and endothelial dysfunction [2], inflammation and atherosclerosis [3] somehow contribute to this matter.”
Background
A potential widespread and important role for sleep-disordered breathing in pressure injury development and delayed healing among those with spinal cord injury
Weintraub, S. J., & Chen, S. X. (2020) · Spinal Cord · doi:10.1038/s41393-020-0434-6 · Cited by 6
Is Vimentin the Cause or Effect of Obstructive Sleep Apnea Development?
Kerget, B., Afşin, D. E., Kerget, F., Aşkın, S., Araz, Ö., & Akgün, M. (2020) · Lung · doi:10.1007/s00408-020-00341-6 · Cited by 6
Increased the circulating levels of malondialdehyde in patients with obstructive sleep apnea: a systematic review and meta-analysis
Fadaei, R., Safari‐Faramani, R., Hosseini, H., Koushki, M., Ahmadi, R., Rostampour, M., & Khazaie, H. (2021) · Sleep And Breathing · doi:10.1007/s11325-021-02293-4 · Cited by 6
Brain Activity after Intermittent Hypoxic Brain Condition in Rats
Mun, B., Jang, Y.-C., Kim, E.-J., Kim, J., & Song, M. (2021) · Brain Sciences · doi:10.3390/brainsci12010052 · Cited by 6
“Functional deficits were also reported and the mechanism triggering these impairments was suggested to be related to neuronal apoptosis and oxygen-free radicals, which may activate a harmful process under a chronic intermittent hypoxic condition [12,13].”
Background
Effects of Intermittent Hypoxia on Neurological Function
Gozal, D. (2009) · Contemporary clinical neuroscience · doi:10.1007/978-1-60327-579-8_9 · Cited by 6
Oxidative Stress – The Culprit of Obstructive Sleep Apnea Syndrome
Lavie, L., & Lavie, P. (2006) · KARGER eBooks · doi:10.1159/000093151 · Cited by 6
Self-citation
[Homocysteine levels in patients with obstructive sleep apnea syndrome].
Yavuz, Z., Ursavaş, A., Eğe, E., İlçöl, Y. Ö., Karadağ, M., Uzaslan, E., & Gözü, R. O. (2008) · PubMed · Cited by 6
Coronary Artery Disease and Obstructive Sleep Apnea
Hedner, J. A., Franklin, K. A., & Peker, Y. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-6645-3.00121-3 · Cited by 6
Biochemical study of idebenone effect on mitochondrial metabolism of yeast
Chapela, S. P., Burgos, H. I., Salazar, A. I., Nievas, I., Kriguer, N., & Stella, C. A. (2007) · Cell Biology International · doi:10.1016/j.cellbi.2007.08.003 · Cited by 6
“On the other hand, there are situations, such as sleep apnea, in which the period of oxygen absence is followed by a normal supply of oxygen (Lavie, 2003; Lavie et al., 2004).”
Background
Novel Role for Reactive Oxygen Species as Amplifiers of Intermittent Hypoxia. Focus on “Reactive Oxygen Species Mediate Central Cardiorespiratory Network Responses to Acute Intermittent Hypoxia”
Prabhakar, N. R. (2007) · Journal of Neurophysiology · doi:10.1152/jn.01322.2006 · Cited by 6
GraphSleepFormer: a multi-modal graph neural network for sleep staging in OSA patients
Wang, C., Jiang, X., Lv, C., Meng, Q., Zhao, P., Di, Y., Feng, C., Xu, F., Lu, S., Jung, T., et al. (2025) · Journal of Neural Engineering · doi:10.1088/1741-2552/adb996 · Cited by 5
“Patients experience apnea and hypoventilation symptoms because of pharyngeal cavity narrowing during sleep, which can lead to systemic hypertension, myocardial infarction, stroke, and other related diseases [2, 3].”
The interaction between comorbidities and sleep stages influences oxygen re‐saturation characteristics
Howarth, T. P., Hietakoste, S., Ebrahimian, S., Rissanen, M., Kainulainen, S., & Karhu, T. (2025) · Journal of Sleep Research · doi:10.1111/jsr.14459 · Cited by 5
“Yet, the re-oxygenation aspect (also termed ‘ re-saturation ’ ) is also hypothesised to cause significant damage via free radicals, but as yet remains largely un-investigated (Lavie, 2003; Perry & Wadhwa, 1988).”
Hypoxia in multiple sclerosis
Burtscher, J., Motl, R. W., Berek, K., Ehrenreich, H., Kopp, M., & Hohenauer, E. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103666 · Cited by 6
“Oxidative stress [168], mitochondrial dysfunction [169], aberrant activation of inducible NO synthase (iNOS) [170] and resultant inflammatory processes are involved in the pathogenesis of OSA and related diseases [171].”
Reduced Inspiratory Muscle Strength in Patients with Type 2 Diabetes Mellitus and Obstructive Sleep Apnoea
Rehling, T., Banghøj, A. M., Kristiansen, M. H., Tarnow, L., & Mølsted, S. (2017) · Journal of Diabetes Research · doi:10.1155/2017/4121794 · Cited by 5
“Furthermore, the oxidative stress that often occurs in patients with OSA could also be expected to play a role in a potential negative impact on the IMS [19].”
Background
Effects of continuous positive airway pressure on resolvin and matrix metalloproteinase-9 in patients with obstructive sleep apnea
Lin, C.-C., Chen, W.-J., Sun, Y.-K., Chiu, C., Lin, M.-W., & Tzeng, I. (2020) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2020.103603 · Cited by 5
Effects of oral appliances on serum cytokines in adults with obstructive sleep apnea: a systematic review
Mecenas, P., Miranda, G. H. N., Fagundes, N. C. F., Normando, D., & Ribeiro, K. C. F. (2021) · Sleep And Breathing · doi:10.1007/s11325-021-02485-y · Cited by 5
Relationship between Sleep Stages and HRV response in Obstructive Sleep Apnea Patients
Romero, D., & Jane, R. (2021) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc46164.2021.9630148 · Cited by 5
“However, some conditions have been associated with this matter including an elevated sympathetic activity of the autonomous nervous system (ANS) [4], oxidative stress [2], inflammation and atherosclerosis [3].”
Background
Molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea
Lin, C.-C., Wang, Y.-P., Chiu, C.-H., Sun, Y.-K., Lin, M., & Tzeng, I. (2022) · The Journal of Laryngology & Otology · doi:10.1017/s0022215121004722 · Cited by 5
Comorbidities and anthropometric parameters in obstructive sleep apnea syndrome: a phenotype-based study
Yeşildağ, M., & Duksal, F. (2025) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2025.2512136 · Cited by 5
“OSAS causes the development and progression of many comorbid diseases such as depression, endocrinological and cardiometabolic diseases, and chronic respiratory diseases (3–6).”
Chronic permanent hypoxemia predisposes to mild elevation of liver stiffness
Tahiri, M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i30.10564 · Cited by 5
Nasal continuous positive airway pressure: influence on digital volume pulse in obstructive sleep apnoea patients
Scholze, A., Lamwers, S., Tepel, M., & Sanner, B. M. (2011) · European Respiratory Journal · doi:10.1183/09031936.00052611 · Cited by 5
Continuous positive airway pressure treatment in patients with OSA
Montserrat, J. M., Navajas, D., Parra, O., & Farré, R. (2010) · European Respiratory Society eBooks · doi:10.1183/1025448x.00025109 · Cited by 5
Obstructive sleep apnea and hypertension: the role of gut microbiome
Šiarnik, P., Klobučníková, K., Mucska, I., Hlucháňová, A., Hanus, O., Turčáni, P., & Kollár, B. (2020) · Vnitřní lékařství · doi:10.36290/vnl.2020.120 · Cited by 5
“Regulácia génu pre eNOS je ovplyvnená saturáciou krvi kyslíkom, pričom hypoxia vedie k zníženiu jeho syntézy K zhoršeniu endoteliálnej funkcie prispieva aj deplécia NO pôsobením oxidačného stresu vznikajúceho v podmienkach IH a reoxygenácie (22).”
Markers of Carotid Plaque Destabilization in Patients With Sleep-Disordered Breathing
Lavie, L., Si-on, E., & Hoffman, A. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.811916 · Cited by 5
“Hence, OSA has been implicated as one of the risk factors inducing atherosclerosis (13, 14).”
BackgroundSelf-citation
Detecting Obstructive Apnea Episodes using Dynamic Bayesian Networks and ECG-based Time-Series
Romero, D., & Jané, R. (2022) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc48229.2022.9870930 · Cited by 5
“This condition has been linked to some cardiovascular consequences, including among others, systemic hypertension, heart failure, coronary artery disease and stroke [1], [2],”
Background
Sleep Disturbances in General Medical Disorders
Chokroverty, S. (2017) · Springer eBooks · doi:10.1007/978-1-4939-6578-6_47 · Cited by 5
Total oxidant–antioxidant and paraoxonase-1 levels in premenstrual dysphoric disorder: a follow-up study
Özcan, H., Oral, E., Güleç, M., Türkez, H., Gulec, T. C., Üstündağ, M. F., Aydınoğlu, Ü., & Yücel, A. (2017) · Psychiatry and Clinical Psychopharmacology · doi:10.1080/24750573.2017.1326735 · Cited by 5
The deleterious effects of chronic obstructive pulmonary disease and obstructive sleep apnea: pathophysiology and implications on treatment
Gharib, A. M. (2020) · Egyptian Journal of Bronchology · doi:10.1186/s43168-020-00026-x · Cited by 5

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)
DOI: 10.1053/smrv.2002.0261
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Obstructive sleep apnoea syndrome – an oxidative stress disorder

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