Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study

Peres, Bernardo Urbanetto; Allen, A J Hirsch; Shah, Aditi; Fox, Nurit; Laher, Ismail; Almeida, Fernanda R.; Jen, Rachel; Ayas, Najib

doi:10.3390/antiox9060476

Cited by 28 publications

(19 citation statements)

References 29 publications

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“…Inflammation plays a pivotal role in the initiation and progression of CVD [9]. In addition, OSA is characterized by intermittent hypoxia and oxidative stress, which in turn activates systemic inflammation [10]; both animals exposed to intermittent hypoxia and patients with OSA have increased levels of inflammatory markers including C-reactive protein (CRP), interleukins, and cellular adhesion molecules [11][12][13]. This inflammation is likely a contributing factor to premature CVD in OSA patients.…”

Section: Introductionmentioning

confidence: 99%

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

et al. 2021

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Background Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD. Research question Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA? Study design and methods Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases. Results 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40–9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16–8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94–11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19–2.38), p-value for interaction = 0.07. Interpretation In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

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Section: Introductionmentioning

confidence: 99%

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

et al. 2021

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“…After a full-text revision of 16 articles, three studies were further excluded because of missing information. Thus, thirteen studies were included in the meta-analysis [ 14 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. A total of 847 OSA patients (mean age 47 years, 74% males) and 438 controls (mean age 50 years, 72% males) were evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…The forest plot for serum/plasma SOD concentrations in OSA patients and controls in the five studies is reported in Figure 5 . In all studies [ 14 , 31 , 32 , 33 , 34 ], OSA patients had lower serum/plasma SOD concentrations compared to controls (mean difference range, −3.24 to −0.18) and the difference was statistically significant in two [ 32 , 33 ]. Extreme heterogeneity between studies was observed (I2 = 98.0%, p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

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Circulating Superoxide Dismutase Concentrations in Obstructive Sleep Apnoea (OSA): A Systematic Review and Meta-Analysis

Pau

Mangoni

Zinellu³

et al. 2021

Antioxidants

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Obstructive Sleep Apnoea (OSA) is characterized by a pro-oxidant state that results from the recurrent hypoxia-reoxygenation cycles. Superoxide dismutase (SOD), a key antioxidant enzyme involved in the detoxification of superoxide radicals, could represent a reliable marker to monitor the antioxidant defences in OSA. In order to capture and critically appraise the available evidence, we performed a systematic review and meta-analysis of studies reporting SOD concentrations in OSA patients and non-OSA controls in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar. In total, 13 studies in 847 OSA patients and 438 non-OSA controls were included in the meta-analysis. Blood SOD concentrations were significantly lower in OSA patients (SMD = 0.87, p < 0.001). By contrast, serum/plasma SOD concentrations were not significantly different between the two groups. Although extreme between-study heterogeneity was observed, the SMD was not substantially modified when individual studies were sequentially removed. In conclusion, we observed that whole blood, but not serum/plasma, SOD concentrations were significantly lower in OSA patients compared with controls. Our meta-analysis suggests an impaired antioxidant defence in OSA that is more robustly assessed in the corpuscular biological matrix and provides useful background information for further studies investigating the association between SOD changes and clinical status in OSA.

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“…Higher rates of oxidative stress have been identified in patients with OSA. Moreover, oxidative stress positively correlates with the severity of OSA [183,184]. It was shown that patients with OSA have significantly higher plasma and urinary levels of Sestrin2.…”

Section: Respiratory Diseasesmentioning

confidence: 99%

Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function

Ala

Eftekhar

2021

Oxidative Medicine and Cellular Longevity

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Sestrin2 is a stress-inducible metabolic regulator and a conserved antioxidant protein which has been implicated in the pathogenesis of several diseases. Sestrin2 can protect against atherosclerosis, heart failure, hypertension, myocardial infarction, stroke, spinal cord injury neurodegeneration, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, acute kidney injury (AKI), chronic kidney disease (CKD), and pulmonary inflammation. Oxidative stress and cellular damage signals can alter the expression of Sestrin2 to compensate for organ damage. Different stress signals such as those mediated by P53, Nrf2/ARE, HIF-1α, NF-κB, JNK/c-Jun, and TGF-β/Smad signaling pathways can induce Sestrin2 expression. Subsequently, Sestrin2 activates Nrf2 and AMPK. Furthermore, Sestrin2 is a major negative regulator of mTORC1. Sestrin2 indirectly regulates the expression of several genes and reprograms intracellular signaling pathways to attenuate oxidative stress and modulate a large number of cellular events such as protein synthesis, cell energy homeostasis, mitochondrial biogenesis, autophagy, mitophagy, endoplasmic reticulum (ER) stress, apoptosis, fibrogenesis, and lipogenesis. Sestrin2 vigorously enhances M2 macrophage polarization, attenuates inflammation, and prevents cell death. These alterations in molecular and cellular levels improve the clinical presentation of several diseases. This review will shed light on the beneficial effects of Sestrin2 on several diseases with an emphasis on underlying pathophysiological effects.

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Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study

Cited by 28 publications

References 29 publications

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

Circulating Superoxide Dismutase Concentrations in Obstructive Sleep Apnoea (OSA): A Systematic Review and Meta-Analysis

Target Sestrin2 to Rescue the Damaged Organ: Mechanistic Insight into Its Function

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