The role inflammatory response genes in obstructive sleep apnea syndrome: a review

Lima, Francisco Fábio Ferreira de; Mazzotti, Diego R.; Tufik, Sérgio; Bittencourt, Lia

doi:10.1007/s11325-015-1226-7

Cited by 77 publications

(45 citation statements)

References 82 publications

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“…5B). These findings are limited by the small sample size but are consistent with prior data examining OSA alone in both children and adults (25)(26)(27) and suggest that there is likely important human relevance to our in vitro findings.…”

Section: Patients With Osa and Nafld Have Higher Levels Of Circulatinsupporting

confidence: 86%

Intermittent hypoxia is a proinflammatory stimulus resulting in IL‐6 expression and M1 macrophage polarization

Schaefer

Mark

et al. 2017

Hepatology Communications

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The biological factors that promote inflammation or nonalcoholic steatohepatitis (NASH) in the setting of nonalcoholic fatty liver disease remain incompletely understood. Clinical studies have demonstrated an association between obstructive sleep apnea (OSA) and both inflammation and fibrosis in NASH, but the mechanism has not been identified. In this study, we use in vitro modeling to examine the impact of intermittent hypoxia on the liver. Hepatocyte, stellate cell, and macrophage cell lines were exposed to intermittent or sustained hypoxia. Candidate genes associated with inflammation, fibrosis, and lipogenesis were analyzed. Circulating cytokines were assessed in human serum of patients with nonalcoholic fatty liver disease. Intermittent hypoxia results in significant induction of interleukin (IL)‐6 expression in both hepatocytes and macrophages. The increase in IL‐6 expression was independent of hypoxia inducible factor 1 induction but appeared to be in part related to antioxidant response element and nuclear factor kappa B activation. Mature microRNA 365 (miR‐365) has been demonstrated to regulate IL‐6 expression, and we found that miR‐365 expression was decreased in the setting of intermittent hypoxia. Furthermore, macrophage cell lines showed polarization to an M1 but not M2 phenotype. Finally, we found a trend toward higher circulating levels of IL‐6 in patients with OSA and NASH. Conclusion: Intermittent hypoxia acts as a potent proinflammatory stimulus, resulting in IL‐6 induction and M1 macrophage polarization. Increased IL‐6 expression may be due to both induction of antioxidant response element and nuclear factor kappa B as well as inhibition of miR‐365 expression. Higher levels of IL‐6 were observed in human samples of patients with OSA and NASH. These findings provide biological insight into mechanisms by which obstructive sleep apnea potentiates inflammation and fibrosis in patients with fatty liver disease. (Hepatology Communications 2017;1:326–337)

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Section: Patients With Osa and Nafld Have Higher Levels Of Circulatinsupporting

confidence: 86%

Intermittent hypoxia is a proinflammatory stimulus resulting in IL‐6 expression and M1 macrophage polarization

Schaefer

Mark

et al. 2017

Hepatology Communications

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“…Systemic inflammation,94–96 oxidative stress,34 endothelial dysfunction,97 and increased sympathetic activity induce hemorheologic alterations with increased cell adhesion molecules, endothelial cell dysfunction, thrombotic factor activation, procoagulant activity,98 and vascular remodeling, all factors contributing to atherosclerotic risk99 and consequent cardiovascular morbidity and mortality. Animal studies suggest that reduction of endothelial-dependent vasodilatation is the most important precursor for atherosclerosis, related to increased oxidative stress with reduced levels of nitric oxide (NO).…”

Section: Deleterious Effects Of Cih: the Osa Modelmentioning

confidence: 99%

Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

Sforza¹,

Roche²

2016

104

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Obstructive sleep apnea (OSA) is a prevalent sleep disorder considered as an independent risk factor for cardiovascular consequences, such as systemic arterial hypertension, ischemic heart disease, cardiac arrhythmias, metabolic disorders, and cognitive dysfunction. The pathogenesis of OSA-related consequence is assumed to be chronic intermittent hypoxia (IH) inducing alterations at the molecular level, oxidative stress, persistent systemic inflammation, oxygen sensor activation, and increase of sympathetic activity. Overall, these mechanisms have an effect on vessel permeability and are considered to be important factors for explaining vascular, metabolic, and cognitive OSA-related consequences. The present review attempts to examine together the research paradigms and clinical studies on the effect of acute and chronic IH and the potential link with OSA. We firstly describe the literature data on the mechanisms activated by acute and chronic IH at the experimental level, which are very helpful and beneficial to explaining OSA consequences. Then, we describe in detail the effect of IH in patients with OSA that we can consider “the human model” of chronic IH. In this way, we can better understand the specific pathophysiological mechanisms proposed to explain the consequences of IH in OSA.

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“…Intriguingly, associations between the 5-HTR2A and IL-6 single nucleotide polymorphisms (SNPs) and OSA have been recently described [34]. Thus, the role of inflammatory response genes in OSA seems to be a critical factor as a pivotal phenomenon that impacts directly the onset of this sleep disorder [35] ( Table 1). …”

Section: Obstructive Sleep Apnea and Genesmentioning

confidence: 99%

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

et al. 2017

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The role inflammatory response genes in obstructive sleep apnea syndrome: a review

Abstract: This review aimed to show an updated view on the studies evaluating the genetic basis of inflammatory response in many aspects of OSAS and to highlight potential research areas not fully explored to date in this field.

Cited by 77 publications

References 82 publications

Intermittent hypoxia is a proinflammatory stimulus resulting in IL‐6 expression and M1 macrophage polarization

Intermittent hypoxia is a proinflammatory stimulus resulting in IL‐6 expression and M1 macrophage polarization

Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

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