Pathobiology of Obstructive Sleep Apnea-Related Dyslipidemia: Focus on the Liver

Mirrakhimov, Aibek E.; Ali, Alaa M.

doi:10.1155/2013/687069

Cited by 16 publications

(13 citation statements)

References 46 publications

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“…Functional enrichment analysis suggested that most of these genes are directly involved in the above-mentioned biological processes ( Figure 2 ), which are highly relevant for OSA. Several pathways found in our study have already been discussed by many authors with inconclusive evidence [ 26 – 33 ] before as well as their involvement in the pathogenesis of OSA. For instance, Diefenbach et al [ 34 ] showed the positive association between EDN1 variant Lys198Asn genotype and OSA.…”

Section: Discussionsupporting

confidence: 50%

Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

Jagannathan

Seixas²,

St-Jules³

et al. 2017

Sleep Disorders

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Rationale Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. The objective of this systematic genetic study is to identify “novel” biomarkers for OSA using systems biology approach. Methods Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO) analyses and candidate genes prioritization were performed using Enrichr tool. Genes pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway Analysis. Results In total, we have identified 153 genes. The top 10 pathways associated with OSA include (i) serotonin receptor interaction, (ii) pathways in cancer, (iii) AGE-RAGE signaling in diabetes, (iv) infectious diseases, (v) serotonergic synapse, (vi) inflammatory bowel disease, (vii) HIF-1 signaling pathway, (viii) PI3-AKT signaling pathway, (ix) regulation lipolysis in adipocytes, and (x) rheumatoid arthritis. After removing the overlapping genes, we have identified 23 candidate genes, out of which >30% of the genes were related to the genes involved in the serotonin pathway. Among these 4 serotonin receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA. Conclusions This preliminary report identifies several potential candidate genes associated with OSA and also describes the possible regulatory mechanisms.

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Section: Discussionsupporting

confidence: 50%

Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

Jagannathan

Seixas²,

St-Jules³

et al. 2017

Sleep Disorders

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“…13,15 Obstructive sleep apnea causes hyperlipidemia by increasing lipid synthesis and decreasing clearance of lipopro-teins. 34 An earlier report suggested a close association between OSA and cardiovascular disease. 44 Research evidence has also suggested that OSA increases the incidence of stroke.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of obstructive sleep apnea worsens the overall outcome of intracranial aneurysm: a pioneer study

Bir

Nanda

Cuéllar

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Obstructive sleep apnea (OSA) is associated with the progression of abdominal and thoracic aortic aneurysms. However, the role of OSA in the overall outcome of intracranial aneurysms (IAs) has not yet been established. Authors of this report investigated the role of OSA in the overall outcome of IAs. METHODS Radiological and clinical data on patients (from 2010 through 2015) with confirmed IA were retrospectively reviewed. Significant differences between the OSA and non-OSA groups were determined using a chi-square test. Logistic regression analysis was performed to identify the predictors of an unfavorable IA outcome. RESULTS Among the 283 patients with confirmed IAs, 45 patients (16%) were positively screened for OSA, a proportion that was significantly higher than the prevalence of OSA in nonaneurysmal neurosurgical patients (4%, p = 0.008). The percentage of patients with hypertension (p = 0.018), a body mass index ≥ 30 kg/m (p < 0.0001), hyperlipidemia (p = 0.034), diabetes mellitus (p = 0.005), chronic heart disease (CHD; p = 0.024), or prior stroke (p = 0.03) was significantly higher in the OSA group than in the non-OSA group. Similarly, the percentage of wide-necked aneurysms (p = 0.00001) and patients with a poor Hunt and Hess Grade IV-V (p = 0.01) was significantly higher in the OSA group than in the non-OSA group. In addition, the percentage of ruptured aneurysms (p = 0.03) and vasospasms (p = 0.03) was significantly higher in the OSA group. The percentage of patients with poor modified Rankin Scale (mRS) scores (3-6) was significantly higher in the OSA group (p = 0.03). A separate cohort of patients with ruptured IAs showed similar results. In both univariate (p = 0.01) and multivariate (p = 0.04) regression analyses, OSA was identified as an individual predictor of an unfavorable outcome. In addition, hypertension and prior stroke were revealed as predictors of a poor IA outcome. CONCLUSIONS Complications of IA such as rupture and vasospasm are often the consequence of uncontrolled OSA. Overall outcome (mRS) of IAs is also affected by the co-occurrence of OSA. Therefore, the coexistence of OSA with IA affects the outcome of IAs. Obstructive sleep apnea is a risk factor for a poor outcome in IA patients.

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“…The mechanism for the impact of IH on lipids may be due to the IH-mediated increases in gene expression of the hypoxia inducible factor family, generation of reactive oxygen species, stearoyl-coenzyme A desaturase-1, altered lipid peroxidation, and sympathetic system dysfunction 379,380. Catecholamines, whose levels are elevated in OSA, modulate the activity of adipocyte hormone-sensitive lipase via their counter-regulatory effects of antagonizing insulin, leading to the lipolysis and consequent breakdown of triglycerides into free fatty acids (FFA) and glycerol, which then will be resynthesized in the liver to form very low density lipoprotein (VLDL) 381. Supporting this putative mechanism, adults with OSA have elevated levels of FFA;382 these nocturnal surges in hepatic FFA production in adults with OSA may accelerate CVD progression and concomitant cardiac dysfunction 383.…”

Section: Obstructive Sleep Apnea and Cardiometabolic Riskmentioning

confidence: 99%

Role of sleep quality in the metabolic syndrome

Koren¹,

Dumin²,

Gozal³

2016

DMSO

142

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Emerging evidence has assigned an important role to sleep as a modulator of metabolic homeostasis. The impact of variations in sleep duration, sleep-disordered breathing, and chronotype to cardiometabolic function encompasses a wide array of perturbations spanning from obesity, insulin resistance, type 2 diabetes, the metabolic syndrome, and cardiovascular disease risk and mortality in both adults and children. Here, we critically and extensively review the published literature on such important issues and provide a comprehensive overview of the most salient pathophysiologic pathways underlying the links between sleep, sleep disorders, and cardiometabolic functioning.

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Pathobiology of Obstructive Sleep Apnea-Related Dyslipidemia: Focus on the Liver

Cited by 16 publications

References 46 publications

Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

Coexistence of obstructive sleep apnea worsens the overall outcome of intracranial aneurysm: a pioneer study

Role of sleep quality in the metabolic syndrome

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