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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Result
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“SDBinduced hypoxemia and its rapid recovery cause oxidative stress, inducing the activation of reactive oxygen speciessensitive transcription factors (nuclear factor-kappa B and activator protein 1) (27), followed by the production of inflammatory cytokines (tumor necrosis factor-α and interleukin-6) (28), which are p…”
Background
Transient receptor potential canonical 5 channel is involved in the cardiac damage related to obstructive sleep apnea-hypopnea syndrome in rats
Wen, W., Yao, Q., Chen, Y., Li, Z., Maitikuerban, B., Zhang, Y., Zhang, J., Simayi, Z., Xu, X., & Zhang, X. (2020) · Annals of Palliative Medicine · doi:10.21037/apm.2020.04.08 · Cited by 12
“In the pro-inflammatory pathways, Ca2+ is an important regulator of ROS production (9), and mitochondria is a known pool of calcium.”
BackgroundInfluential
Overweight explains the increased red blood cell aggregation in patients with obstructive sleep apnea
Sinnapah, S., Cadélis, G., Xavier Waltz, A., Lamarre, Y., & Connes, P. (2015) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-121655 · Cited by 12
“The underlying mechanisms are under investigation but inflammation [20, 24, 30], endothelial dysfunction [8], oxidative stress [11, 28] and hypercoagulation [52] could participate in increasing the risk for cardiovascular disorders.”
Adenosine Receptor Blockade by Caffeine Inhibits Carotid Sinus Nerve Chemosensory Activity in Chronic Intermittent Hypoxic Animals
Sacramento, J. F., González, C., Gonzalez-Martin, M. C., & Conde, S. V. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-18440-1_15 · Cited by 12
Neck circumference and blood pressure among children: a systematic review and meta-analysis
Moradi, S., Mohammadi, H., Ghavami, A., & Rouhani, M. H. (2018) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2018.10.007 · Cited by 12
Endothelium-derived markers and antioxidant status in the blood of obstructive sleep apnea males
Cofta, S., Wysocka, E., Michalak, S., Piorunek, T., Batura‐Gabryel, H., & Torliński, L. (2009) · European journal of medical research · doi:10.1186/2047-783x-14-s4-49 · Cited by 12
“Key words: obstructive sleep apnea, total antioxidant status, endothelium, E-selectin”
Background
A machine learning approach for the diagnosis of obstructive sleep apnoea using oximetry, demographic and anthropometric data
Leong, Z. H., Loh, S. R. H., Leow, L. C., Ong, T. H., & Toh, S. T. (2023) · Singapore Medical Journal · doi:10.4103/singaporemedj.smj-2022-170 · Cited by 11
“[11,12] While pulse oximetry is used for the diagnosis of OSA in the paediatric population because of its high PPV, the negative predictive value (NPV) is very low.”
Intermittent hypoxia: linkage between OSAS and epilepsy
Ma, Y., & Wu, Q. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1230313 · Cited by 11
“Hypoxia-induced elevated production of ROS can be attributed to several factors, including mitochondrial dysfunction, activation of NADPH oxidase (NOX) and xanthine oxidase, and uncoupling of nitric oxide synthase (NOS) (Lavie, 2003; Lavie, 2015).”
Background
Pediatric Obstructive Sleep Apnea: Neurocognitive Consequences
Chandrakantan, A., & Adler, A. C. (2019) · Current anesthesiology reports · doi:10.1007/s40140-019-00331-2 · Cited by 11
Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients
Sánchez‐Armengol, Á., López, P. V., Caballero‐Eraso, C., Carmona-Bernal, C., Asensio-Cruz, M. I., Barbé, F., & Capote, F. (2015) · Sleep And Breathing · doi:10.1007/s11325-014-1115-5 · Cited by 11
“Patients suffering from OSA have shown less antioxidant capacity, as expressed by lower levels of vitamins A and E and a reduced plasma total antioxidant status, including decreased GGT levels [5, 10].”
Background
Detection of sleep apnea events via tracking nonlinear dynamic cardio-respiratory coupling from electrocardiogram signals
Karandikar, K., Le, T., Sa-ngasoongsong, A., Wongdhamma, W., & Bukkapatnam, S. (2013) · International IEEE/EMBS Conference on Neural Engineering · doi:10.1109/ner.2013.6696194 · Cited by 11
Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding
Sharma, R. K., Otsuka, M., Gaba, G., & Mehta, S. (2012) · RSC Advances · doi:10.1039/c2ra21852f · Cited by 11
The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet
Wang, H., Tian, J., Feng, S., Sun, N., Chen, B.-Y., & Zhang, Y. (2012) · Sleep And Breathing · doi:10.1007/s11325-012-0784-1 · Cited by 12
Oxidative Stress and Sleep Apnea-Hypopnea Syndrome
Barceló, A., & Barbé, F. (2005) · Archivos de Bronconeumología · doi:10.1016/s1579-2129(06)60248-6 · Cited by 11
Sleep apnea is linked to heart failure, but does treatment improve outcome?
WEXLER, L. F., & Javaheri, S. M. (2005) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.72.10.929 · Cited by 11
Sleep apnoea syndrome today: much done, more to do
McNicholas, W. T. (2003) · Sleep Medicine Reviews · doi:10.1053/smrv.2002.0265 · Cited by 11
Metabolipidomic Analysis in Patients with Obstructive Sleep Apnea Discloses a Circulating Metabotype of Non-Dipping Blood Pressure
Pinilla, L., Benitez, I. D., Gràcia‐Lavedan, E., Torres, G., Mínguez, O., Vaca, R., Jové, M., Sol, J., Pamplona, R., Barbé, F., et al. (2023) · Antioxidants · doi:10.3390/antiox12122047 · Cited by 11
“The repetitive cycles of hypoxia and reoxygenation experienced in OSA are considered to be analogous to repeated ischemia–reperfusion injury [4], resulting in an increased production of reactive oxygen species (ROS) that exceeds the antioxidant supply [5,6].”
Background
Identifying key antioxidative stress factors regulating Nrf2 in the genioglossus with human umbilical cord mesenchymal stem-cell therapy
Guo, H., Liu, Y., Yu, X., Tian, N., Liu, Y., & Yu, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-55103-8 · Cited by 10
“OSAHS-associated oxidative stress is caused by an increase in the pro-oxidation/antioxidant ratio, mainly due to the production of hypoxia during apnea events and the formation of reactive oxygen species (ROS) during re-oxygenation in respiratory recovery 19 .”
Background
Narcolepsy and risk of cardiovascular outcomes beyond stimulant use
Riaz, M., Bhattacharjee, R., Lo‐Ciganic, W., Wilson, D. L., Wickwire, E. M., Malhotra, A., Kaufmann, C. N., & Park, H. (2025) · SLEEP · doi:10.1093/sleep/zsaf197 · Cited by 11
Obstructive Sleep Apnea and Metabolic Syndrome
Tasali, E., & Ip, M. (2012) · Proceedings of the American Thoracic Society · Cited by 10
Using clinical data to predict obstructive sleep apnea
He, S., Li, Y., Xu, W., & Han, D. (2022) · Journal of Thoracic Disease · doi:10.21037/jtd-20-3139 · Cited by 8
“7 central obesity witnessed nocturnal apnea tonsillar size lateral narrowing × + × + × + × − [2]”
Background
Prevalence of symptoms and risk of sleep apnea in patients with ruptured cerebral aneurysm
Alaqeel, A. M., Almasri, S. H., Alotaibi, N. M., AlYamany, M., BaHammam, A. S., Mohammad, Y. M., & Sharif, M. M. (2013) · Neurosciences · doi:10.17712/1658-3183.2024 · Cited by 10
Impact of age on intermittent hypoxia in obstructive sleep apnea: a propensity-matched analysis
Bostancı, A., Bozkurt, S., & Turhan, M. (2017) · Sleep And Breathing · doi:10.1007/s11325-017-1560-z · Cited by 10
Aortic Knob Width as a Novel Indicator of Atherosclerosis and Obstructive Sleep Apnea
Tomita, Y., Kasai, T., Ishiwata, S., Daida, H., & Narui, K. (2019) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.50286 · Cited by 10
Risk factors for obstructive sleep apnea-related hypertension in police officers in Southern China
Pan, M., Ou, Q., Chen, B., Hong, Z., & Liu, H. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.09.83 · Cited by 10
“Previous studies of OSA-related hypertension have focused on its pathogenesis (8,9), effectiveness of treatment (10,11), or other aspects of the health condition.”
Background
The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis
Chen, Q., Chen, L., Chen, M., Wu, Y., Zeng, H., Hu, M., Zhang, W., Zheng, Y.-F., & Lin, Q. (2019) · Sleep And Breathing · doi:10.1007/s11325-019-01998-x · Cited by 10
Postprandial glucose and HbA1c are associated with severity of obstructive sleep apnoea in non-diabetic obese subjects
Cignarelli, A., Ciavarella, A., Barbaro, M. P. F., Kounaki, S., Trani, A. D., Falcone, V. A., Quaranta, V. N., Natalicchio, A., Laviola, L., Resta, O., et al. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-021-01602-8 · Cited by 10
“Several mechanisms, including direct effects of hypoxia [31], oxidative stress [32, 33] sympathetic nervous system activation [34] and the associated increase in catecholamines [34–37], and alterations in pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-a [38] and hypoxia-inducible factor-1a [39…”
Background
Proinflammatory and prothrombotic status in emphysematous rats exposed to intermittent hypoxia.
Li, C., Xiao-kun, Y., Feng, J., Lei, P., & Wang, Y. (2015) · Europe PMC (PubMed Central) · Cited by 10
Cardiovascular consequences of obstructive sleep apnea
Suri, J. C., & Sen, M. K. (2013) · Indian Journal of Sleep Medicine · doi:10.5958/j.0974-0155.8.1.003 · Cited by 10
Correlation between the severity of apnea and hypopnea sleep, hypertension and serum lipid and glycemic: a case control study
de Sousa‐Rodrigues, C. F., & Lira, A. B. (2014) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-014-3076-5 · Cited by 10
“The cycles of hypoxia and reoxygenation may alter oxidative balance and induce an increase of free radicals, which are important factors for pathological consequences of OSA [8].”
Background
Influence of Hispanic Ethnicity in Prevalence of Diabetes Mellitus in Sleep Apnea and Relationship to Sleep Phase
Surani, S., Aguilar, R., Komari, V., Surani, A., & Subramanian, S. (2009) · Postgraduate Medicine · doi:10.3810/pgm.2009.09.2057 · Cited by 10
Effect of garlic on rats with chronic intermittent hypoxia combined with diabetes mellitus
Peng, Y., & Hu, K. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8568 · Cited by 10
“All of the above studies indicate that OSAHS is one of the causes of DM. OSAHS is associated with stimulation of oxidative stress (OS) (16).”
Effects of continuous positive airway pressure on exhaled transforming growth factor-β and vascular endothelial growth factor in patients with obstructive sleep apnea
Lin, C.-C., Liaw, S., Chiu, C., & Lin, M.-W. (2020) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.12.55 · Cited by 9
“55 Introduction Severe obstructive sleep apnea (OSA) is characterized by repeated upper airway obstructions (1), intermittent hypoxia, increase sympathetic tone and a significant reduction in rapid eye movement (REM) sleep (1).”
Background
Nocturnal oxygen resaturation parameters are associated with cardiorespiratory comorbidities
Howarth, T. P., Sillanmäki, S., Karhu, T., Rissanen, M., Íslind, A. S., Hrubos‐Strøm, H., de Chazal, P., Huovila, J., Kainulainen, S., & Leppänen, T. (2024) · Sleep Medicine · doi:10.1016/j.sleep.2024.03.047 · Cited by 9
Association between obstructive sleep apnea and multiple adverse clinical outcomes: evidence from an umbrella review
Wang, Q., Zeng, H., Dai, J., Zhang, M., & Shen, P. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1497703 · Cited by 9
The impact of continuous positive airway pressure treatment on retinal vascular changes in obstructive sleep apnea
Wong, B., Tong, J. Y., Schulz, A. M., Graham, S. L., Farah, C. S., & Fraser, C. L. (2021) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.9118 · Cited by 10
Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent
Drummond, S. E., Burns, D. P., Maghrani, S. E., Ziegler, O., Healy, V., & O’Halloran, K. D. (2023) · Cells · doi:10.3390/cells12141834 · Cited by 10
“Oxidative stress is a predominant feature of OSAS with the reactive oxygen species (ROS) produced as a result of recurrent hypoxia/reoxygenation cycles having detrimental consequences for a plethora of integrative bodily systems, highlighting a therapeutic role for antioxidants [8].”
Background
Impact of medications on cognitive function in obstructive sleep apnea syndrome
Lal, C., Siddiqi, N. A., Kumbhare, S., & Strange, C. (2015) · Sleep And Breathing · doi:10.1007/s11325-014-1105-7 · Cited by 9
Which place of pharmacological approaches beyond continuous positive airway pressure to treat vascular disease related to obstructive sleep apnea?
Gautier‐Veyret, E., Pépin, J., & Stanke‐Labesque, F. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.12.006 · Cited by 11
“In humans, similar results have been obtained, with reduced nitric oxide production (assessed by measuring total nitrate and nitrite in plasma) (Alonso-Fernández et al., 2009; Lavie, 2003) and increased plasma endothelin-1 levels in OSA patients (Gjørup et al.”
Background

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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