Chen Yung-Lung, Chen Yung-Che, Chang Ya-Ting, Wang Hui-Ting, Liu Wen-Hao, Chong Shaur-Zheng, Lin Pei-Ting, Hsu Po-Yuan, Su Mao-Chang, Lin Meng-Chih
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Biomedicines. 2021 Oct 13;9(10):1463. doi: 10.3390/biomedicines9101463.
Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on expression. A total of 129 patients were recruited for this study; 26 were excluded due to an AHI < 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]); < 0.001). expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all < 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with expression in HL-1 cells, which offers a hint that may play a crucial role in the development of AF in patients with OSAS.
阻塞性睡眠呼吸暂停综合征（OSAS）是心房颤动（AF）的一个重要危险因素。编码连接蛋白43的基因是心脏缝隙连接中的一种主要蛋白质，在心脏的同步收缩和心律失常中起关键作用。然而，关于其表达在OSAS患者AF发生率中的作用知之甚少。所有前瞻性纳入的OSAS患者均接受了多导睡眠图、心电图、24小时动态心电图检查和超声心动图检查。中度至重度OSAS定义为呼吸暂停低通气指数（AHI）≥15。从所有OSAS患者的血浆中纯化外泌体，并在HL-1细胞中孵育，以研究有AF和无AF患者的外泌体对其表达的影响。本研究共招募了129名患者；26名因AHI<15被排除。在纳入的103名患者中，21名有AF，82名无AF。多变量分析显示，糖尿病、较低的睡眠效率、较低的左心室射血分数和较大的左心房（LA）大小是OSAS患者AF发生的独立预测因素。预测OSAS患者AF发生的LA大小≥38.5mm时，受试者操作特征曲线下面积为0.795（95%置信区间[0.666，0.925]；P<0.001）。在控制年龄和性别后，与无AF患者的外泌体孵育的HL-1细胞中的表达低于与有AF患者的外泌体孵育的HL-1细胞中的表达，并且与AHI和氧去饱和指数（ODI）呈负相关，尤其是在有AF的OSAS患者的非快速眼动期（NREM）（均P<0.05）。LA大小是OSAS患者AF发生的独立预测因素。有AF的OSAS患者NREM期的AHI和ODI与HL-1细胞中的表达呈负相关，这提示其可能在OSAS患者AF的发生发展中起关键作用。
