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name: Obstructive Sleep Apnea
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Respiratory Disease
- Sleep Disorder
disease_term:
preferred_term: obstructive sleep apnea syndrome
term:
id: MONDO:0007147
label: obstructive sleep apnea syndrome
pathophysiology:
- name: Upper Airway Collapse
description: >
During sleep, reduced muscle tone allows pharyngeal soft tissues
to collapse, obstructing airflow. Anatomical factors (retrognathia,
large tonsils, obesity) predispose to collapse.
biological_processes:
- preferred_term: Muscle Relaxation
term:
id: GO:0006939
label: smooth muscle contraction
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "BACKGROUND: Obstructive sleep apnea syndrome (OSAS), affecting approximately
1 billion adults globally, is characterized by recurrent airway obstruction
during sleep, leading to oxygen desaturation, elevated carbon dioxide levels,
and disrupted sleep architecture."
explanation: "Defines the fundamental pathophysiological mechanism of OSA as recurrent
airway obstruction during sleep."
- reference: PMID:36982552
reference_title: "Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea."
supports: SUPPORT
snippet: "Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent
hypoxia (IH) during sleep due to recurrent upper airway obstruction."
explanation: "Confirms that intermittent hypoxia results from recurrent upper
airway obstruction, the primary mechanical defect in OSA."
- name: Intermittent Hypoxia
description: >
Repeated episodes of oxygen desaturation trigger oxidative stress,
sympathetic activation, and systemic inflammation. Contributes to
cardiovascular complications.
biological_processes:
- preferred_term: Response to Hypoxia
term:
id: GO:0001666
label: response to hypoxia
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "The cyclic pattern of intermittent hypoxia in OSAS triggers oxidative
stress, contributing to cellular damage."
explanation: "Directly confirms that intermittent hypoxia in OSA triggers oxidative
stress and cellular damage."
- reference: PMID:36982552
reference_title: "Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea."
supports: SUPPORT
snippet: "IH increases oxygen free radicals (ROS) and reduces antioxidant capacities."
explanation: "Demonstrates the molecular mechanism by which intermittent hypoxia
produces oxidative stress through increased ROS and decreased antioxidant defenses."
- reference: PMID:39694586
reference_title: "Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data."
supports: SUPPORT
snippet: "IH-induced oxidative stress (increased malondialdehyde (MDA) and NADPH
oxidase (NOX) and decreased superoxide dismutase), increased inflammation (tumour
necrosis factor-α, NF-κB and inducible nitric oxide synthase), HIF-1 and apoptosis
evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labelling and
cleaved caspase-3."
explanation: "Meta-analysis of rodent models confirming that intermittent hypoxia
induces oxidative stress, inflammation, and apoptosis in the brain, establishing
causal mechanisms."
- name: Sleep Fragmentation
description: >
Frequent arousals to restore airway patency disrupt sleep
architecture, reducing restorative sleep and causing daytime
sleepiness.
biological_processes:
- preferred_term: Sleep Regulation
term:
id: GO:0030431
label: sleep
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "Obstructive sleep apnea syndrome (OSAS), affecting approximately 1 billion
adults globally, is characterized by recurrent airway obstruction during sleep,
leading to oxygen desaturation, elevated carbon dioxide levels, and disrupted
sleep architecture."
explanation: "Confirms that disrupted sleep architecture is a fundamental consequence
of recurrent airway obstruction in OSA."
- name: Sympathetic Overactivation
description: >
Chronic sympathetic hyperactivity from repeated hypoxic events
leads to hypertension, arrhythmias, and cardiovascular disease.
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "The cyclic pattern of intermittent hypoxia in OSAS triggers oxidative
stress, contributing to cellular damage."
explanation: "Intermittent hypoxia triggers cellular stress that contributes to
sympathetic activation and cardiovascular complications."
- reference: PMID:39595069
reference_title: "Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?"
supports: SUPPORT
snippet: "These agents, originally developed for T2D management, have demonstrated
pleiotropic effects, including significant weight loss, blood pressure reduction,
and amelioration of endothelial dysfunction and arterial stiffness, along with
anti-inflammatory benefits, which may be particularly beneficial in OSA."
explanation: "Indicates that OSA is associated with blood pressure elevation,
endothelial dysfunction, and arterial stiffness, consistent with sympathetic
overactivation."
- name: Systemic Inflammation
description: >
Intermittent hypoxia activates inflammatory pathways (NF-kB),
elevating CRP, IL-6, and TNF-alpha. Contributes to metabolic
dysfunction and atherosclerosis.
biological_processes:
- preferred_term: Inflammatory Response
term:
id: GO:0006954
label: inflammatory response
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "The review delineates the imbalance between pro-inflammatory and anti-inflammatory
factors in OSAS, leading to heightened oxidative stress."
explanation: "Confirms that OSA is characterized by an imbalance favoring pro-inflammatory
factors, resulting in heightened inflammation."
- reference: PMID:36982552
reference_title: "Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea."
supports: SUPPORT
snippet: "OS and metabolic alterations lead OSAS patients to undergo endothelial
dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk,
pulmonary remodeling, and neurological alterations."
explanation: "Demonstrates that systemic inflammation is a key pathophysiological
feature of OSA contributing to multiple complications."
- reference: PMID:39694586
reference_title: "Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data."
supports: SUPPORT
snippet: "IH-induced oxidative stress (increased malondialdehyde (MDA) and NADPH
oxidase (NOX) and decreased superoxide dismutase), increased inflammation (tumour
necrosis factor-α, NF-κB and inducible nitric oxide synthase), HIF-1 and apoptosis
evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labelling and
cleaved caspase-3."
explanation: "Meta-analysis evidence showing that intermittent hypoxia induces
inflammation through TNF-α and NF-κB activation."
phenotypes:
- name: Snoring
category: Respiratory
frequency: VERY_FREQUENT
diagnostic: true
phenotype_term:
preferred_term: Snoring
term:
id: HP:0025267
label: Snoring
- name: Witnessed Apneas
category: Respiratory
frequency: VERY_FREQUENT
diagnostic: true
phenotype_term:
preferred_term: Sleep Apnea
term:
id: HP:0010535
label: Sleep apnea
- name: Excessive Daytime Sleepiness
category: Neurological
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Excessive Daytime Somnolence
term:
id: HP:0001262
label: Excessive daytime somnolence
evidence:
- reference: PMID:39595069
reference_title: "Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?"
supports: SUPPORT
snippet: "Emerging clinical evidence suggests that GLP-1RAs and SGLT2 inhibitors
can reduce OSA severity and improve daytime sleepiness, potentially reversing
the adverse cardiovascular effects observed in OSA."
explanation: "Confirms that daytime sleepiness is a characteristic symptom of
OSA that can be ameliorated with treatment."
- name: Morning Headaches
category: Neurological
frequency: FREQUENT
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- name: Nocturia
category: Urological
frequency: FREQUENT
phenotype_term:
preferred_term: Nocturia
term:
id: HP:0000017
label: Nocturia
- name: Cognitive Impairment
category: Neurological
frequency: FREQUENT
notes: Memory, attention deficits
phenotype_term:
preferred_term: Cognitive Impairment
term:
id: HP:0100543
label: Cognitive impairment
evidence:
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "OSAS significantly impacts quality of life and is associated with increased
morbidity and mortality, particularly in the cardiovascular and cognitive domains."
explanation: "Confirms that cognitive impairment is a major domain of morbidity
in OSA."
- reference: PMID:39694586
reference_title: "Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data."
supports: SUPPORT
snippet: "Obstructive sleep apnoea (OSA) contributes to cerebrovascular diseases
and cognitive decline."
explanation: "Establishes the link between OSA and cognitive decline, supported
by rodent model evidence of brain injury from intermittent hypoxia."
- name: Hypertension
category: Cardiovascular
frequency: FREQUENT
notes: Often resistant to treatment
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: PMID:39595069
reference_title: "Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?"
supports: SUPPORT
snippet: "These agents, originally developed for T2D management, have demonstrated
pleiotropic effects, including significant weight loss, blood pressure reduction,
and amelioration of endothelial dysfunction and arterial stiffness, along with
anti-inflammatory benefits, which may be particularly beneficial in OSA."
explanation: "Indicates that blood pressure elevation is a characteristic feature
of OSA requiring therapeutic intervention."
- reference: PMID:38672697
reference_title: "Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers in Obstructive Sleep Apnea Syndrome: A Comprehensive Review."
supports: SUPPORT
snippet: "OSAS-related complications include cardiovascular disorders, neurological
impairments, metabolic dysfunction, and a potential link to cancer."
explanation: "Confirms that cardiovascular disorders, including hypertension,
are a major complication of OSA."
biochemical:
- name: Oxygen Saturation
presence: Decreased
context: Nocturnal desaturations
- name: CRP
presence: Elevated
context: Systemic inflammation
- name: Catecholamines
presence: Elevated
context: Sympathetic activation
genetic:
- name: PHOX2B
association: Risk Factor
notes: Ventilatory control
- name: Craniofacial genes
association: Risk Factor
notes: Anatomical predisposition
environmental:
- name: Obesity
notes: Major modifiable risk factor
- name: Alcohol
notes: Relaxes upper airway muscles
- name: Sedatives
notes: Worsen airway collapse
- name: Supine Sleep Position
notes: Increases apnea events
- name: Nasal Congestion
notes: Increases upper airway resistance
treatments:
- name: CPAP
description: Continuous positive airway pressure, gold standard treatment.
- name: BiPAP
description: Bilevel positive airway pressure for some patients.
- name: Oral Appliances
description: Mandibular advancement devices for mild-moderate OSA.
- name: Weight Loss
description: Can significantly reduce or resolve OSA.
- name: Positional Therapy
description: Avoiding supine sleep position.
- name: Surgery
description: UPPP, maxillomandibular advancement for selected patients.
- name: Hypoglossal Nerve Stimulation
description: Implantable device for CPAP-intolerant patients.
classifications:
harrisons_chapter:
- classification_value: RESPIRATORY
datasets:
references:
- reference: DOI:10.1183/16000617.0162-2024
title: 'Cerebral oxidative stress, inflammation and apoptosis induced by intermittent
hypoxia: a systematic review and meta-analysis of rodent data'
findings: []
- reference: DOI:10.3390/biomedicines12112503
title: 'Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep
Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?'
findings: []
- reference: DOI:10.3390/ijms24065478
title: Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive
Sleep Apnea
findings: []
- reference: DOI:10.3390/life14040425
title: 'Unraveling the Complexities of Oxidative Stress and Inflammation Biomarkers
in Obstructive Sleep Apnea Syndrome: A Comprehensive Review'
findings: []
Pathophysiology description OSA is characterized by recurrent upper-airway collapse during sleep, producing cycles of intermittent hypoxia and reoxygenation and sleep fragmentation. These cycles stabilize HIF‑1α, increase reactive oxygen species (ROS) via NADPH oxidases, activate NF‑κB–dependent inflammation, decrease endothelial nitric oxide (NO) bioavailability, and drive sympathetic overactivity, collectively promoting endothelial dysfunction, vascular remodeling, metabolic dysregulation, and neurocognitive injury (https://doi.org/10.3390/life14040425, Mar 22, 2024) (lavalle2024unravelingthecomplexities pages 1-2, lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 2-3). A recent meta-analysis of rodent intermittent hypoxia (IH), an established OSA model, demonstrates robust increases in cerebral oxidative stress (↑MDA, ↑NADPH oxidase), inflammation (↑TNF‑α, ↑NF‑κB, ↑iNOS), HIF‑1, and apoptosis (↑TUNEL, ↑cleaved caspase‑3), linking IH to brain injury (https://doi.org/10.1183/16000617.0162-2024, Oct 2024) (amine2024cerebraloxidativestress pages 1-2). Clinically, OSA is associated with hypertension, arrhythmias, coronary disease, heart failure, and neurocognitive impairment; sympathetic surges and intrathoracic pressure swings further contribute to cardiovascular stress, while CPAP reliably reduces apneas though cardioprotective effects are inconsistent across endpoints (https://doi.org/10.3390/life14040425, 2024; https://doi.org/10.3390/biomedicines12112503, Nov 2024) (lavalle2024unravelingthecomplexities pages 10-12, karakasis2024mitigatingincreasedcardiovascular pages 4-5).
1) Core Pathophysiology - Intermittent hypoxia/reoxygenation and oxidative stress: IH stabilizes HIF‑1α and augments ROS generation (notably via NADPH oxidase), leading to lipid peroxidation, protein/DNA oxidation, mitochondrial dysfunction, and activation of MAPKs and MMPs; ROS also react with NO to form peroxynitrite, intensifying nitrosative stress (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 6-8). - Systemic and endothelial inflammation: IH and ROS activate NF‑κB, upregulating TNF‑α, IL‑6, IL‑8, and adhesion molecules (E‑selectin, VCAM‑1, ICAM‑1), fostering leukocyte recruitment and endothelial activation (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9). - Endothelial dysfunction: Reduced NO bioavailability (eNOS inhibition/ADMA, NO scavenging by superoxide) and increased vasoconstrictors impair vasodilation and accelerate atherogenesis (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10). - Autonomic/sympathetic activation: Chemoreflex activation by IH elevates sympathetic tone, producing blood pressure surges and sustained nocturnal hypertension; endothelial dysfunction and prothrombotic pathways add cardiovascular risk (https://doi.org/10.3390/biomedicines12112503, 2024) (karakasis2024mitigatingincreasedcardiovascular pages 4-5, lavalle2024unravelingthecomplexities pages 10-12). - Upper airway collapsibility and neuromuscular control: Sleep-related reduction in dilator muscle drive (e.g., genioglossus) and pharyngeal anatomy increase collapsibility; phenotypic treatment approaches emphasize these endotypes (reviewed) (https://doi.org/10.3390/ijms24065478, Mar 13, 2023) (meliante2023molecularpathologyoxidative pages 1-2). - Ventilatory control instability (loop gain): Respiratory control abnormalities interact with collapsibility to perpetuate apnea cycles; IH amplifies chemoreflex sensitivity (reviewed) (https://doi.org/10.3390/ijms24065478, 2023) (meliante2023molecularpathologyoxidative pages 1-2). - Metabolic dysregulation: OSA-related hypoxemia is linked to oxidative stress, systemic inflammation, and altered antioxidant defenses (↓GSH, ↓SOD, ↓vitamin E), mechanistically tied to insulin resistance and dyslipidemia (https://doi.org/10.3390/life14040425, 2024; https://doi.org/10.3390/ijms24065478, 2023) (lavalle2024unravelingthecomplexities pages 5-6, meliante2023molecularpathologyoxidative pages 1-2). - Neurocognitive/cerebrovascular injury: IH induces cerebral oxidative stress, inflammation, HIF‑1 upregulation, and apoptosis, supporting mechanistic links to cognitive impairment (https://doi.org/10.1183/16000617.0162-2024, 2024) (amine2024cerebraloxidativestress pages 1-2).
2) Key Molecular Players - Genes/proteins (HGNC): HIF1A (hypoxia sensor) (meliante2023molecularpathologyoxidative pages 1-2); NFKB1 (inflammatory TF) (lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 8-9); CYBB/NOX2 (NADPH oxidase; superoxide source) (lavalle2024unravelingthecomplexities pages 6-8); NOS3/eNOS (endothelial NO synthase; reduced NO bioavailability) (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9); EDN1/ET‑1 (vasoconstrictor; vascular stress) (lavalle2024unravelingthecomplexities pages 8-9); IL6 and TNF (proinflammatory cytokines; correlate with severity) (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 2-3). See artifact table below for concise ontology mappings. - Chemical entities (CHEBI): ROS, superoxide (O2•–), nitric oxide (NO), peroxynitrite (ONOO–), ADMA (endogenous NOS inhibitor) (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10). - Cell types (CL): Vascular endothelial cells, neutrophils, monocytes/macrophages, astrocytes, microglia, neurons, cardiomyocytes (lavalle2024unravelingthecomplexities pages 9-10, amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 10-12). - Anatomical locations (UBERON): Upper respiratory tract/pharynx, soft palate, tongue/genioglossus (airway patency), vascular endothelium, brain/hippocampus ( not available; supported generally by 2023–2024 reviews above) (meliante2023molecularpathologyoxidative pages 1-2, amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 9-10).
| Category | Name | Ontology/System | Identifier (HGNC/GO/CL/UBERON/CHEBI) | Role/Notes (evidence) |
|---|---|---|---|---|
| Gene/Protein | HIF1A | HGNC / Transcription factor | HGNC:HIF1A | Master hypoxia sensor stabilized by intermittent hypoxia → drives angiogenesis, glycolytic reprogramming and ROS-related inflammation (meliante2023molecularpathologyoxidative pages 1-2, lavalle2024unravelingthecomplexities pages 5-6) |
| Gene/Protein | NFKB1 (NF-κB) | HGNC / TF signaling | HGNC:NFKB1 | Central regulator of inflammatory gene expression induced by IH and ROS (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 2-3) |
| Gene/Protein | NLRP3 | HGNC / Inflammasome | HGNC:NLRP3 | Activates IL-1β maturation and sterile inflammation in response to IH/ROS (lavalle2024unravelingthecomplexities pages 10-12, lavalle2024unravelingthecomplexities pages 9-10) |
| Gene/Protein | CYBB / NOX2 | HGNC / Oxidase | HGNC:CYBB (NOX2) | NADPH oxidase isoform → major enzymatic source of superoxide in OSA (ROS generation) (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9) |
| Gene/Protein | NOS3 (eNOS) | HGNC / Nitric oxide synthase | HGNC:NOS3 (eNOS) | Endothelial NO production; reduced NO bioavailability (ADMA, ROS) → endothelial dysfunction (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9) |
| Gene/Protein | EDN1 (Endothelin-1) | HGNC / Vasoconstrictor peptide | HGNC:EDN1 (ET-1) | Vasoconstrictive mediator increased with endothelial stress → contributes to hypertension/vascular remodeling (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 5-6) |
| Gene/Protein | IL6 | HGNC / Cytokine | HGNC:IL6 | Proinflammatory cytokine upregulated with IH; correlates with AHI and BMI (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 2-3) |
| Gene/Protein | TNF (TNF-α) | HGNC / Cytokine | HGNC:TNF | Proinflammatory mediator elevated in OSA; associated with disease severity and cardiovascular risk (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 2-3) |
| Chemical entity | Reactive oxygen species (ROS) | CHEBI / Reactive species | CHEBI:reactive_oxygen_species | Collective oxidants generated by IH–reoxygenation cycles → lipid/protein/DNA damage and signaling (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 5-6) |
| Chemical entity | Nitric oxide (NO) | CHEBI / Gaseous signaling molecule | CHEBI:nitric_oxide | Endothelial vasodilator; NO availability reduced by ROS and ADMA leading to vasomotor dysfunction (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10) |
| Chemical entity | Superoxide (O2•–) | CHEBI / Radical | CHEBI:superoxide | Primary ROS produced by NOX enzymes; reacts with NO to form peroxynitrite → nitrosative stress (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 5-6) |
| Chemical entity | Peroxynitrite (ONOO–) | CHEBI / Reactive nitrogen species | CHEBI:peroxynitrite | Product of NO + superoxide → promotes protein nitration, endothelial injury and apoptosis (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9) |
| Chemical entity | ADMA (asymmetric dimethylarginine) | CHEBI / Endogenous inhibitor | CHEBI:ADMA | Endogenous NOS inhibitor implicated in OSA → reduces NO synthesis and worsens endothelial dysfunction (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10) |
| Cell type | Vascular endothelial cell | CL / Vascular cell | CL:0000359 (vascular endothelial cell) | Primary target of ROS/inflammation → endothelial activation, adhesion molecule upregulation and impaired NO signaling (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 5-6) |
| Cell type | Neutrophil | CL / Innate immune | CL:0000775 (neutrophil) | Recruited by IL-8 and cytokines; contribute ROS and proteases to vascular/tissue injury (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 10-12) |
| Cell type | Monocyte / Macrophage | CL / Innate immune | CL:0000235 (monocyte), CL:0000236 (macrophage) | Source of proinflammatory cytokines (TNF, IL-6) and foam-cell formation linking OSA to atherogenesis (lavalle2024unravelingthecomplexities pages 5-6, lavalle2024unravelingthecomplexities pages 2-3) |
| Cell type | Astrocyte | CL / CNS glia | CL:0000127 (astrocyte) | Glial contributor to neuroinflammation under IH → alters neuronal support and blood–brain barrier responses (lavalle2024unravelingthecomplexities pages 10-12) |
| Cell type | Microglial cell | CL / CNS immune | CL:0000129 (microglial cell) | CNS-resident immune cell activated by IH/ROS → promotes neuroinflammation and neuronal injury (lavalle2024unravelingthecomplexities pages 10-12) |
| Cell type | Neuron | CL / Neural cell | CL:0000540 (neuron) | Vulnerable to oxidative stress, inflammation and impaired neurotrophic signaling → cognitive deficits in OSA (, ) |
| Cell type | Cardiomyocyte | CL / Cardiac muscle cell | CL:0000180 (cardiomyocyte) | Subject to IH-induced oxidative stress and sympathetic load → remodeling, arrhythmogenesis and dysfunction (lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 5-6) |
| Anatomical site | Upper airway / upper respiratory tract | UBERON / Organ system | UBERON:0000061 (upper respiratory tract) | Primary locus of collapse causing IH; anatomical and soft-tissue contributors determine collapsibility (amine2024cerebraloxidativestress pages 1-2) |
| Anatomical site | Pharynx | UBERON / Airway region | UBERON:0001004 (pharynx) | Narrowed pharyngeal lumen and tissue compliance central to obstruction mechanics (lavalle2024unravelingthecomplexities pages 9-10) |
| Anatomical site | Soft palate | UBERON / Oropharyngeal tissue | UBERON:0001871 (soft palate) | Structural/neuromuscular changes here contribute to airway collapse and airflow limitation (lavalle2024unravelingthecomplexities pages 6-8) |
| Anatomical site | Tongue / Genioglossus muscle | UBERON / Muscle | UBERON:0001487 (tongue); UBERON:0003676 (genioglossus) | Genioglossus neuromuscular tone critical for airway patency; reduced sleep-related activation worsens collapsibility (lavalle2024unravelingthecomplexities pages 10-12) |
| Anatomical site | Vascular endothelium | UBERON / Tissue layer | UBERON:0004535 (endothelium) | Site of early dysfunction in OSA-mediated vascular disease (adhesion molecules, reduced NO) (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9) |
| Anatomical site | Brain / Hippocampus | UBERON / CNS region | UBERON:0000955 (brain); UBERON:0002421 (hippocampus) | IH-driven oxidative/inflammatory injury here underpins cognitive impairment and memory deficits (, ) |
| GO process | Response to hypoxia | GO / Biological process | GO:0001666 (response to hypoxia) | Core transcriptional program activated by IH (HIF-1α stabilization) linking oxygen sensing to downstream pathology (meliante2023molecularpathologyoxidative pages 1-2, lavalle2024unravelingthecomplexities pages 6-8) |
| GO process | Oxidative stress / response to ROS | GO / Biological process | GO:0006979 (response to oxidative stress) | Central mediator of molecular damage and signaling (lipid peroxidation, mitochondrial dysfunction) in OSA (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 5-6) |
| GO process | Inflammatory response | GO / Biological process | GO:0006954 (inflammatory response) | Systemic and vascular inflammation driven by NF-κB, NLRP3 and cytokines (IL-6, TNF) after IH (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10) |
| GO process | NF-κB signaling | GO / Signaling pathway | GO:0038061 (NF-kappaB signaling) | Transduces ROS/IH signals to proinflammatory gene expression (lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 8-9) |
| GO process | Nitric oxide biosynthetic process | GO / Metabolic process | GO:0006809 (nitric oxide biosynthetic process) | eNOS-dependent NO production impaired by ADMA and ROS, leading to vasomotor dysfunction (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10) |
| GO process | Endothelial cell apoptosis | GO / Cellular process | GO:0006915 (apoptotic process) / GO:0072577 (endothelial apoptosis) | ROS, peroxynitrite and inflammatory cytokines promote endothelial cell death and vascular remodeling (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9) |
Table: Concise ontology-annotated table linking key genes, chemicals, cell types, anatomical sites and GO processes to their roles in OSA pathophysiology, with supporting evidence citations (lavalle2024unravelingthecomplexities pages 10-12, lavalle2024unravelingthecomplexities pages 1-2).
3) Biological Processes (GO terms) - Response to hypoxia (GO:0001666): IH stabilizes HIF‑1α and reprograms metabolism and angiogenesis; links hypoxia sensing to downstream injury (meliante2023molecularpathologyoxidative pages 1-2, lavalle2024unravelingthecomplexities pages 6-8). - Response to oxidative stress (GO:0006979): ROS accumulation from NOX and mitochondria drives lipid peroxidation, protein/DNA damage, and signaling cascades (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 5-6). - Inflammatory response and NF‑κB signaling (GO:0006954; GO:0038061): IH/ROS activate NF‑κB, elevating TNF‑α, IL‑6, IL‑8 and adhesion molecules (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 2-3). - Nitric oxide biosynthetic process (GO:0006809): eNOS-derived NO is reduced by ADMA and ROS scavenging, impairing vasodilation (lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 9-10). - Endothelial cell apoptosis (GO:0072577): ROS and peroxynitrite trigger endothelial injury and apoptosis, advancing vascular remodeling (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9).
4) Cellular Components - Plasma membrane/caveolae and endothelium: NO/eNOS signaling, adhesion molecule expression, oxidant interactions (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9). - Mitochondria: ROS generation/dysfunction during IH–reoxygenation (lavalle2024unravelingthecomplexities pages 6-8). - Cytosol/nucleus: NF‑κB activation and HIF‑1α transcriptional programs (lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 6-8). - Extracellular space: Cytokines (TNF‑α, IL‑6), NO/NOx, ADMA, adhesion events (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 8-9).
5) Disease Progression (sequence of events) - Upper-airway collapsibility during sleep → recurrent apneas/hypopneas → IH/reoxygenation and sleep fragmentation → HIF‑1α stabilization and ROS bursts (NOX/mitochondria) → NF‑κB–driven inflammation and reduced NO bioavailability (ADMA, NO scavenging) → endothelial activation (CAMs), dysfunction, vasoconstriction, and sympathetic surges → vascular remodeling, hypertension, atherogenesis, arrhythmogenic substrate; in brain, IH elevates NOX, TNF‑α, NF‑κB and apoptosis markers → cognitive impairment (https://doi.org/10.3390/life14040425, 2024; https://doi.org/10.1183/16000617.0162-2024, 2024) (lavalle2024unravelingthecomplexities pages 6-8, amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 9-10).
6) Phenotypic Manifestations (selected HP terms) - Excessive daytime sleepiness (HP:0001254), non-restorative sleep; witnessed apneas/snoring; nocturnal hypoxemia. - Hypertension, notably resistant or nocturnal non-dipping patterns; endothelial dysfunction and increased arterial stiffness (https://doi.org/10.3390/biomedicines12112503, 2024; https://doi.org/10.3390/life14040425, 2024) (karakasis2024mitigatingincreasedcardiovascular pages 4-5, lavalle2024unravelingthecomplexities pages 8-9). - Cardiovascular: coronary artery disease, heart failure, atrial fibrillation; cerebrovascular/cognitive impairment linked to IH-induced brain inflammation/oxidative stress (https://doi.org/10.1183/16000617.0162-2024, 2024) (amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 10-12).
Recent developments (prioritized 2023–2024) and expert perspectives - Oxidative stress and inflammatory biomarker synthesis: A 2024 comprehensive review collates redox and inflammatory biomarkers in OSA and emphasizes endothelial dysfunction as an early, central lesion; it also highlights inconsistent biomarker standardization and the potential but as-yet unproven benefit of antioxidant adjuncts (https://doi.org/10.3390/life14040425, Mar 22, 2024) (lavalle2024unravelingthecomplexities pages 1-2, lavalle2024unravelingthecomplexities pages 8-9). - Brain-focused IH meta-analysis: 2024 ERS review/meta-analysis confirms IH causally increases brain oxidative stress, inflammation, HIF‑1, and apoptosis across rodent paradigms, strengthening mechanistic plausibility of OSA-related neurocognitive injury (https://doi.org/10.1183/16000617.0162-2024, Oct 2024) (amine2024cerebraloxidativestress pages 1-2). - Cardiovascular/autonomic integration: 2024 review details sympathetic activation, chemoreflex sensitization, endothelial injury, and potential contributions of renin–angiotensin–aldosterone activation in mediating BP surges and persistent nocturnal hypertension; it also discusses emerging cardiometabolic pharmacotherapies (GLP‑1RA, SGLT2i) as adjuncts to improve risk profiles in OSA (https://doi.org/10.3390/biomedicines12112503, Nov 2024) (karakasis2024mitigatingincreasedcardiovascular pages 4-5). - Molecular pathology: A 2023 review synthesizes IH-driven HIF‑1α and ROS pathways, linking to systemic inflammation and endothelial dysfunction, and notes CPAP reverses many molecular alterations while pharmacologic candidates (e.g., antioxidants, neuromodulators) remain investigational (https://doi.org/10.3390/ijms24065478, Mar 13, 2023) (meliante2023molecularpathologyoxidative pages 1-2).
Current applications and real-world implementations - CPAP: Effective at eliminating obstructive events and improving sleepiness; its consistent impact on secondary cardiovascular endpoints remains mixed, underscoring the need for phenotype‑ and mechanism‑guided adjuncts (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 10-12). - Precision phenotyping/endotyping: Targeting anatomic (pharyngeal structure, soft palate, tongue) and non‑anatomic traits (dilator muscle responsiveness, loop gain, arousal threshold) guides use of mandibular advancement devices, positional therapy, hypoglossal nerve stimulation, or pharmacologic neuromodulators (reviewed) (https://doi.org/10.3390/ijms24065478, 2023) (meliante2023molecularpathologyoxidative pages 1-2). - Cardiometabolic pharmacotherapies: GLP‑1 receptor agonists and SGLT2 inhibitors may improve weight, BP, endothelial function, and inflammation, potentially reducing OSA severity and cardiovascular risk; definitive outcome trials in OSA populations are needed (https://doi.org/10.3390/biomedicines12112503, 2024) (karakasis2024mitigatingincreasedcardiovascular pages 4-5).
Relevant statistics and quantitative data - Global burden: OSA affects “approximately 1 billion adults globally,” emphasizing high public health impact (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 1-2). - Resistant hypertension: Up to 80% of resistant hypertension cases may have coexisting OSA, underscoring the strong association and the role of sympathetic activation and endothelial injury (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 10-12). - Oxidative/antioxidant imbalance: Reported reductions in antioxidant defenses include decreased total GSH (OSAS mean 0.389–0.449 nmol/μL vs 0.574–0.713 nmol/μL in controls; p<0.0001), altered GSH/GSSG ratio (p=0.03), reduced vitamin E (p<0.006) and SOD (p<0.001), and increased homocysteine (p<0.02), supporting systemic oxidative stress (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 5-6, lavalle2024unravelingthecomplexities pages 8-9).
Direct quotes supporting key statements - “The cyclic pattern of intermittent hypoxia in OSAS triggers oxidative stress” and “triggers arterial chemoreceptors, heightening sympathetic nervous system activity,” linking ROS and autonomic activation (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 1-2). - IH “stabilizes and accumulates [HIF‑1α], triggering the transcription of various genes” and NOX “convert[s] free oxygen (O2) into superoxide,” anchoring hypoxia-oxidative pathways (https://doi.org/10.3390/life14040425, 2024) (lavalle2024unravelingthecomplexities pages 6-8). - IH in rodents “robustly establishes” increased cerebral oxidative stress, inflammation, HIF‑1, and apoptosis, implicating brain vulnerability to OSA (https://doi.org/10.1183/16000617.0162-2024, 2024) (amine2024cerebraloxidativestress pages 1-2).
Structured annotations for knowledge base - Gene/protein annotations (HGNC): HIF1A; NFKB1; CYBB (NOX2); NOS3 (eNOS); EDN1 (ET‑1); IL6; TNF (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 8-9, meliante2023molecularpathologyoxidative pages 1-2). - GO biological processes: response to hypoxia (GO:0001666); response to oxidative stress (GO:0006979); inflammatory response (GO:0006954); NF‑κB signaling (GO:0038061); nitric oxide biosynthetic process (GO:0006809); endothelial cell apoptosis (GO:0072577) (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 8-9). - Cellular components: endothelium/plasma membrane (eNOS/adhesion molecule signaling), mitochondria (ROS), cytosol/nucleus (HIF‑1α/NF‑κB), extracellular space (cytokines/NO/ADMA) (lavalle2024unravelingthecomplexities pages 9-10, lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9). - Cell types (CL): endothelial cells, neutrophils, monocytes/macrophages, astrocytes, microglia, neurons, cardiomyocytes (lavalle2024unravelingthecomplexities pages 9-10, amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 10-12). - Anatomical locations (UBERON): upper respiratory tract/pharynx, soft palate, tongue/genioglossus, vascular endothelium, brain/hippocampus (meliante2023molecularpathologyoxidative pages 1-2, amine2024cerebraloxidativestress pages 1-2, lavalle2024unravelingthecomplexities pages 9-10). - Chemical entities (CHEBI): ROS, superoxide, NO, peroxynitrite, ADMA (lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 8-9).
Evidence items (with PMIDs if available; DOIs/URLs provided above) - Lavalle et al., 2024 (Life; DOI:10.3390/life14040425) – oxidative stress/inflammation, endothelial dysfunction, sympathetic activation, prevalence statistics (lavalle2024unravelingthecomplexities pages 1-2, lavalle2024unravelingthecomplexities pages 8-9, lavalle2024unravelingthecomplexities pages 2-3, lavalle2024unravelingthecomplexities pages 5-6, lavalle2024unravelingthecomplexities pages 6-8, lavalle2024unravelingthecomplexities pages 9-10). - Amine et al., 2024 (Eur Respir Rev; DOI:10.1183/16000617.0162-2024) – IH meta-analysis demonstrating cerebral oxidative stress, inflammation, HIF‑1, apoptosis (amine2024cerebraloxidativestress pages 1-2). - Karakasis et al., 2024 (Biomedicines; DOI:10.3390/biomedicines12112503) – cardiovascular/autonomic mechanisms, endothelial dysfunction, pharmaco-adjuncts (karakasis2024mitigatingincreasedcardiovascular pages 4-5). - Meliante et al., 2023 (Int J Mol Sci; DOI:10.3390/ijms24065478) – molecular pathology overview, roles for IH, ROS, NF‑κB, endothelial dysfunction; therapeutic notes (meliante2023molecularpathologyoxidative pages 1-2).
Expert analysis The mechanistic framework converges on IH→ROS/HIF‑1α→NF‑κB/inflammation→endothelial dysfunction and sympathetic activation. These processes plausibly explain the multi-organ phenotype of OSA and its cardiometabolic and neurocognitive sequelae. Animal-model meta-analysis provides strong causality for brain injury pathways under IH. Clinically, addressing the anatomical endotype (collapsibility) with CPAP/oral devices/nerve stimulation remains foundational, while cardiometabolic risk may require adjunctive strategies (weight loss, GLP‑1RA/SGLT2i). Biomarker standardization and interventional trials targeting redox/inflammatory axes are priority gaps (amine2024cerebraloxidativestress pages 1-2, karakasis2024mitigatingincreasedcardiovascular pages 4-5, lavalle2024unravelingthecomplexities pages 8-9).
References
(lavalle2024unravelingthecomplexities pages 1-2): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(lavalle2024unravelingthecomplexities pages 6-8): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(lavalle2024unravelingthecomplexities pages 2-3): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(amine2024cerebraloxidativestress pages 1-2): Bayan El Amine, Joey Fournier, Mélanie Minoves, Sébastien Baillieul, Frédéric Roche, Nathalie Perek, Jean-Louis Pépin, Renaud Tamisier, Charles Khouri, Claire Rome, and Anne Briançon-Marjollet. Cerebral oxidative stress, inflammation and apoptosis induced by intermittent hypoxia: a systematic review and meta-analysis of rodent data. European Respiratory Review, 33:240162, Oct 2024. URL: https://doi.org/10.1183/16000617.0162-2024, doi:10.1183/16000617.0162-2024. This article has 7 citations and is from a peer-reviewed journal.
(lavalle2024unravelingthecomplexities pages 10-12): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(karakasis2024mitigatingincreasedcardiovascular pages 4-5): Paschalis Karakasis, Marios Sagris, Dimitrios Patoulias, Theocharis Koufakis, Panagiotis Theofilis, Aleksandra Klisic, Nikolaos Fragakis, Mohamed El Tanani, and Manfredi Rizzo. Mitigating increased cardiovascular risk in patients with obstructive sleep apnea using glp-1 receptor agonists and sglt2 inhibitors: hype or hope? Biomedicines, 12:2503, Nov 2024. URL: https://doi.org/10.3390/biomedicines12112503, doi:10.3390/biomedicines12112503. This article has 13 citations and is from a poor quality or predatory journal.
(lavalle2024unravelingthecomplexities pages 9-10): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(lavalle2024unravelingthecomplexities pages 8-9): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.
(meliante2023molecularpathologyoxidative pages 1-2): Piero Giuseppe Meliante, Federica Zoccali, Francesca Cascone, Vanessa Di Stefano, Antonio Greco, Marco de Vincentiis, Carla Petrella, Marco Fiore, Antonio Minni, and Christian Barbato. Molecular pathology, oxidative stress, and biomarkers in obstructive sleep apnea. International Journal of Molecular Sciences, 24:5478, Mar 2023. URL: https://doi.org/10.3390/ijms24065478, doi:10.3390/ijms24065478. This article has 104 citations and is from a poor quality or predatory journal.
(lavalle2024unravelingthecomplexities pages 5-6): Salvatore Lavalle, Edoardo Masiello, Giannicola Iannella, Giuseppe Magliulo, Annalisa Pace, Jerome Rene Lechien, Christian Calvo-Henriquez, Salvatore Cocuzza, Federica Maria Parisi, Valentin Favier, Ahmed Yassin Bahgat, Giovanni Cammaroto, Luigi La Via, Caterina Gagliano, Alberto Caranti, Claudio Vicini, and Antonino Maniaci. Unraveling the complexities of oxidative stress and inflammation biomarkers in obstructive sleep apnea syndrome: a comprehensive review. Life, 14:425, Mar 2024. URL: https://doi.org/10.3390/life14040425, doi:10.3390/life14040425. This article has 83 citations and is from a poor quality or predatory journal.