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

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 476
Author(s):  
Bernardo U. Peres ◽  
AJ Hirsch Allen ◽  
Aditi Shah ◽  
Nurit Fox ◽  
Ismail Laher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Smoking History ◽  
Obstructive Sleep ◽  
History Of ◽  
Statin Usage ◽  
The Impact

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.

The Impact of Chronic Intermittent Hypoxia on Cardiac Performance of Patients With Obstructive Sleep Apnea and Cardiovascular Disease

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 1058A
Author(s):  
Faisal Siddiqui ◽  
Madalina Macrea ◽  
Mitchell Horowitz ◽  
Thomas Martin ◽  
Tomer Pelleg ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiac Performance ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact

Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome

2007 ◽  
Vol 293 (4) ◽  
pp. R1666-R1670 ◽  
Author(s):  
Walter T. McNicholas
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Cpap Therapy ◽  
Obstructive Sleep ◽  
Cardiovascular Morbidity And Mortality ◽  
Apnea Syndrome ◽  
The Impact

Considerable evidence is now available of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease. The association is particularly strong for systemic arterial hypertension, but there is growing evidence of an association with ischemic heart disease and stroke. The mechanisms underlying cardiovascular disease in patients with OSAS are still poorly understood. However, the pathogenesis is likely to be a multifactorial process involving a diverse range of mechanisms, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation, and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. Therapy with continuous positive airway pressure (CPAP) has been associated with significant benefits to cardiovascular morbidity and mortality, both in short-term studies addressing specific aspects of morbidity, such as hypertension, and more recently in long-term studies that have evaluated major outcomes of cardiovascular morbidity and mortality. However, there is a clear need for further studies evaluating the impact of CPAP therapy on cardiovascular outcomes. Furthermore, studies on the impact of CPAP therapy have provided useful information concerning the role of basic cell and molecular mechanisms in the pathophysiology of OSAS.

Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice

2007 ◽  
Vol 102 (5) ◽  
pp. 1806-1814 ◽  
Author(s):  
Ah-Mee Park ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O2 and 2 min 21% O2) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H2O2 scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.

scholarly journals Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia

2015 ◽  
Vol 118 (5) ◽  
pp. 544-557 ◽  
Author(s):  
Diane C. Lim ◽  
Daniel C. Brady ◽  
Pengse Po ◽  
Li Pang Chuang ◽  
Laise Marcondes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mouse Model ◽  
Mouse Models ◽  
Intermittent Hypoxia ◽  
Molecular Signatures ◽  
Rodent Models ◽  
Obstructive Sleep ◽  
And Oxidative Stress

Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12- iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12- iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions.

scholarly journals Edaravone mitigates cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome via regulation of cAMP/PKACREB pathway

2021 ◽  
Vol 20 (11) ◽  
pp. 2299-2304
Author(s):  
Yongmei Zhao ◽  
Hongli Li ◽  
Yong Chen ◽  
Kexing Li ◽  
Sufei Yang
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
New Drugs ◽  
Juvenile Rats ◽  
Protein Levels ◽  
Obstructive Sleep ◽  
Hypopnea Syndrome

Purpose: To investigate the influence of edaravone on cognitive impairment and hippocampal injury in juvenile rats with obstructive sleep apnea hypopnea syndrome (OSAHS), and the mechanism involved.Methods: Fifty-four young Wistar rats were randomly selected into control, intermittent hypoxia and edaravone groups. The contents of the antioxidants CAT, Mn-SOD, Cu/Zn SOD and oxidative stress products malondialdehyde (MDA) in hippocampus were assayed and compared. The expressions of brain-derived neurotrophic factor (BDNF), Bcl-2, CREB, p-CREB and PKAc were determined.Results: The times taken to cross the target quadrant and the platform; levels of CAT and Mn-SOD, as well as protein levels of BNDF, Bcl-2, p-CREB and PKAc were markedly lower in intermittent hypoxia group than in controls; and MDA contents, 8-OHdG and protein hydroxyl were markedly higher in intermittent hypoxic rats group than in controls. Time taken to cross the platform and quadrant; activities of CAT and Mn-SOD, and protein concentrations of BDNF, Bcl-2, p-CREB and PKAc were markedly higher in the edaravone-treated rats than in intermittent hypoxia rats.Conclusion: Edaravone significantly mitigated cognitive damage and hippocampal lesions in OSAHS rats via a mechanism related to alleviation of oxidative stress and up-regulation of the expressions of p-CREB and its downstream proteins BDNF and Bcl-2. This finding provides a theoretical basis for research and development of new drugs against OSAHS.

scholarly journals Intermittent Hypoxia and Hypercapnia, a Hallmark of Obstructive Sleep Apnea, Alters the Gut Microbiome and Metabolome

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Anupriya Tripathi ◽  
Alexey V. Melnik ◽  
Jin Xue ◽  
Orit Poulsen ◽  
Michael J. Meehan ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Gut Microbiome ◽  
Intermittent Hypoxia ◽  
Joint Analysis ◽  
Gut Microbes ◽  
Causal Pathways ◽  
Obstructive Sleep ◽  
Cardiometabolic Disorders ◽  
The Impact

ABSTRACTObstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2(hypoxia) and high CO2(hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2and CO2can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences. Here, we model human OSA and its cardiovascular consequence usingLdlr−/−mice fed a high-fat diet and exposed to intermittent hypoxia and hypercapnia (IHH). The gut microbiome and metabolome were characterized longitudinally (using 16S rRNA amplicon sequencing and untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) and seen to covary during IHH. Joint analysis of microbiome and metabolome data revealed marked compositional changes in both microbial (>10%, most remarkably inClostridia) and molecular (>22%) species in the gut. Moreover, molecules that altered in abundance included microbe-dependent bile acids, enterolignans, and fatty acids, highlighting the impact of IHH on host-commensal organism cometabolism in the gut. Thus, we present the first evidence that IHH perturbs the gut microbiome functionally, setting the stage for understanding its involvement in cardiometabolic disorders.IMPORTANCEIntestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders.

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