Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

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Abstract

Background

Obstructive sleep apnea (OSA) is a disease seriously threatening individual health, which results in serious complications such as hypertension and stroke. These complications are associated with oxidative stress triggered by intermittent hypoxia in OSA. Sestrin2 is a crucial factor involved in oxidative stress. The goal of this study was to investigate if a relationship exists between OSA and Sestrin2.

Methods

We prospectively enrolled 71 subjects, and 16 patients of them with severe OSA completed 4 weeks of nasal continuous positive airway pressure (nCPAP) therapy. We measured and compared the concentration of Sestrin2 in the urine of all subjects, as well as the changes between before and after nCPAP treatment. Additionally, the correlation between Sestrin2 and sleep parameters was analyzed, and the multiple linear regression analysis with stepwise selection was performed to explore the relationship between Sestrin2 and various factors.

Results

A total of 71 subjects were enrolled and divided into two groups: OSA group ( n = 41), control group ( n = 30). The level of urinary Sestrin2 in OSA patients was significantly higher than that of the control group, and increased with the severity of OSA, while it reduced after nCPAP treatment. Additionally, Sestrin2 was positively correlated with apnea/hypopnea index (AHI), oxygen desaturation index, oxygen saturation < 90% percentage of recording time spent (PRTS) and high-density lipoprotein (HDL), while negatively correlated with the lowest oxygen saturation. Importantly, Sestrin2 was independently associated with AHI, oxygen saturation < 90% PRTS and HDL.

Conclusions

Urinary Sestrin2 is involved in OSA, and is a paramount marker of OSA severity.

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Most cited references 36

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Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea.

Karl Franklin, Eva Hellstrom-Lindberg (2015)

The prevalence of obstructive sleep apnea (OSA) defined at an apnea-hypopnea index (AHI) ≥5 was a mean of 22% (range, 9-37%) in men and 17% (range, 4-50%) in women in eleven published epidemiological studies published between 1993 and 2013. OSA with excessive daytime sleepiness occurred in 6% (range, 3-18%) of men and in 4% (range, 1-17%) of women. The prevalence increased with time and OSA was reported in 37% of men and in 50% of women in studies from 2008 and 2013 respectively. OSA is more prevalent in men than in women and increases with age and obesity. Smoking and alcohol consumption are also suggested as risk factors, but the results are conflicting. Excessive daytime sleepiness is suggested as the most important symptom of OSA, but only a fraction of subjects with AHI >5 report daytime sleepiness and one study did not find any relationship between daytime sleepiness and sleep apnea in women. Stroke and hypertension and coronary artery disease are associated with sleep apnea. Cross-sectional studies indicate an association between OSA and diabetes mellitus. Patients younger than 70 years run an increased risk of early death if they suffer from OSA. It is concluded that OSA is highly prevalent in the population. It is related to age and obesity. Only a part of subjects with OSA in the population have symptoms of daytime sleepiness. The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design and characteristics of included subjects including effects of the obesity epidemic. Cardiovascular disease, especially stroke is related to OSA, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA.

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Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage.

Dongmin Kang, Sue Rhee, S. Sung … (2013)

Sestrins (Sesns) protect cells from oxidative stress. The mechanism underlying the antioxidant effect of Sesns has remained unknown, however. The Nrf2-Keap1 pathway provides cellular defense against oxidative stress by controlling the expression of antioxidant enzymes. We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the antioxidant function of Sesns is mediated through activation of Nrf2 in a manner reliant on p62-dependent autophagic degradation of Keap1. Sesn2 was upregulated in the liver of mice subjected to fasting or subsequent refeeding with a high-carbohydrate, fat-free diet, whereas only refeeding promoted Keap1 degradation and Nrf2 activation, because only refeeding induced p62 expression. Ablation of Sesn2 blocked Keap1 degradation and Nrf2 activation induced by refeeding and thereby increased the susceptibility of the liver to oxidative damage resulting from the acute stimulation of lipogenesis associated with refeeding. Copyright © 2013 Elsevier Inc. All rights reserved.

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Diabetes and mortality following acute coronary syndromes.

Debra Murphy, Alastair Stewart, Satishkumar Mohanavelu … (2007)

The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain. To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS. A subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62,036 patients (46,577 with ST-segment elevation myocardial infarction [STEMI] and 15,459 with unstable angina/non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event. Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes. Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI (2.1% vs 1.1%, P < .001) and STEMI (8.5% vs 5.4%, P < .001). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with higher 30-day mortality after UA/NSTEMI (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.24-2.56) or STEMI (OR, 1.40; 95% CI, 1.24-1.57). Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI (hazard ratio [HR], 1.65; 95% CI, 1.30-2.10) or STEMI (HR, 1.22; 95% CI, 1.08-1.38). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2% vs 8.1%). Despite modern therapies for ACS, diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease.

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Author and article information

Contributors

Shibo Sun:

ORCID: http://orcid.org/0000-0001-9287-1820

shibosunky@126.com

Journal

Journal ID (nlm-ta): Lung

Journal ID (iso-abbrev): Lung

Title: Lung

Publisher: Springer US (New York )

ISSN (Print): 0341-2040

ISSN (Electronic): 1432-1750

Publication date (Electronic): 15 February 2019

Publication date PMC-release: 15 February 2019

Publication date (Print): 2019

Volume: 197

Issue: 2

Pages: 123-129

Affiliations

[1 ]GRID grid.414902.a, Department of Respiratory and Critical Care Medicine, , First Affiliated Hospital, Kunming Medical University, ; Kunming, China

[2 ]ISNI 0000 0000 9588 0960, GRID grid.285847.4, 2015 Innovation Class, , Kunming Medical University, ; Kunming, China

[3 ]Obstetrical Department, Zhengzhou Maternity and Child Care Center, Zhengzhou, China

[4 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Department of Respiratory Medicine, Beijing Friendship Hospital, , Capital Medical University, ; Beijing, China

[5 ]ISNI 0000 0000 9588 0960, GRID grid.285847.4, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, , Kunming Medical University, ; Kunming, China

Author information

Shibo Sun http://orcid.org/0000-0001-9287-1820

Article

Publisher ID: 205

DOI: 10.1007/s00408-019-00205-8

PMC ID: 6486896

PubMed ID: 30770985

SO-VID: 25e503f4-17f7-462a-bb9a-ba76607e2c0d

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 9 October 2018

Date accepted : 7 February 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100007846, Yunnan Provincial Department of Education;

Award ID: No. 2017zzx201

Award Recipient : Shibo Sun

Funded by: Teaching and Reform Program of Kunming Medical University

Award ID: Nos. 2016-JY-Y-43

Award ID: 2017-JY-Y-040

Award Recipient : Shibo Sun

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: sestrin2,obstructive sleep apnea,apnea/hypopnea index,high-density lipoprotein

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: sestrin2, obstructive sleep apnea, apnea/hypopnea index, high-density lipoprotein

Investigation of Urinary Sestrin2 in Patients with Obstructive Sleep Apnea

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Abstract

Background

Methods

Results

Conclusions

Related collections

Inflamed lung in vitro co-culture models

Most cited references 36

Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea.

Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage.

Diabetes and mortality following acute coronary syndromes.

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