The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, th...

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Main Authors: Yung-Lung Chen, Yung-Che Chen, Hui-Ting Wang, Ya-Ting Chang, Yen-Nan Fang, Shukai Hsueh, Wen-Hao Liu, Pei-Ting Lin, Po-Yuan Hsu, Mao-Chang Su, Kuo-Tung Huang, Meng-Chih Lin
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/12/2/148
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author Yung-Lung Chen
Yung-Che Chen
Hui-Ting Wang
Ya-Ting Chang
Yen-Nan Fang
Shukai Hsueh
Wen-Hao Liu
Pei-Ting Lin
Po-Yuan Hsu
Mao-Chang Su
Kuo-Tung Huang
Meng-Chih Lin
author_facet Yung-Lung Chen
Yung-Che Chen
Hui-Ting Wang
Ya-Ting Chang
Yen-Nan Fang
Shukai Hsueh
Wen-Hao Liu
Pei-Ting Lin
Po-Yuan Hsu
Mao-Chang Su
Kuo-Tung Huang
Meng-Chih Lin
author_sort Yung-Lung Chen
collection DOAJ
description Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO<sub>2</sub>, mean SpO<sub>2</sub>, and LA size (all <i>p</i> < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all <i>p</i> < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all <i>p</i> < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all <i>p</i> < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO<sub>2</sub> and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO<sub>2</sub> and HIF-1α (all <i>p</i> < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.
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spelling doaj.art-3535c5fd01024fd88d02c92c6ce5c1ee2023-11-23T20:44:51ZengMDPI AGLife2075-17292022-01-0112214810.3390/life12020148The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea SyndromeYung-Lung Chen0Yung-Che Chen1Hui-Ting Wang2Ya-Ting Chang3Yen-Nan Fang4Shukai Hsueh5Wen-Hao Liu6Pei-Ting Lin7Po-Yuan Hsu8Mao-Chang Su9Kuo-Tung Huang10Meng-Chih Lin11Department of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanSchool of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanSchool of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanSchool of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDepartment of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Internal Medicine, Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanSchool of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanObstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO<sub>2</sub>, mean SpO<sub>2</sub>, and LA size (all <i>p</i> < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all <i>p</i> < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all <i>p</i> < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all <i>p</i> < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO<sub>2</sub> and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO<sub>2</sub> and HIF-1α (all <i>p</i> < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.https://www.mdpi.com/2075-1729/12/2/148intermittent hypoxemialeft atrial remodelingobstructive sleep apnea syndromeinflammation
spellingShingle Yung-Lung Chen
Yung-Che Chen
Hui-Ting Wang
Ya-Ting Chang
Yen-Nan Fang
Shukai Hsueh
Wen-Hao Liu
Pei-Ting Lin
Po-Yuan Hsu
Mao-Chang Su
Kuo-Tung Huang
Meng-Chih Lin
The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
Life
intermittent hypoxemia
left atrial remodeling
obstructive sleep apnea syndrome
inflammation
title The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
title_full The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
title_fullStr The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
title_full_unstemmed The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
title_short The Impact of Intermittent Hypoxemia on Left Atrial Remodeling in Patients with Obstructive Sleep Apnea Syndrome
title_sort impact of intermittent hypoxemia on left atrial remodeling in patients with obstructive sleep apnea syndrome
topic intermittent hypoxemia
left atrial remodeling
obstructive sleep apnea syndrome
inflammation
url https://www.mdpi.com/2075-1729/12/2/148
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