GJA1 Expression and Left Atrial Remodeling in the Incidence of Atrial Fibrillation in Patients with Obstructive Sleep Apnea Syndrome.

Yung-Lung Chen,Ya-Ting Chang,Wen-Hao Liu,Pei-Ting Lin,Shaur-Zheng Chong,Po-Yuan Hsu,Hui-Ting Wang,Yung-Che Chen,Meng-Chih Lin,Mao-Chang Su

doi:10.3390/biomedicines9101463

Yung-Lung Chen, Ya-Ting Chang + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines9101463

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Abstract

Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 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 GJA1 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 GJA1 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]); p < 0.001). GJA1 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 p < 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 GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS.

Highlights

Atrial fibrillation (AF) is one of the most common heart diseases
We found there was a negative correlation between GJA1 gene expression and apnea-hypopnea index (AHI) during total sleep time (TST) (r = −0.458, p = 0.037), AHI during non-rapid eye movement (NREM)
We found there was a negative correlation between GJA1 gene expression and AHI during TST (r = −0.458, p = 0.037), AHI during non-rapid eye movement (NREM) (r = −0.467, p = 0.033), oxygen desaturation index (ODI) during TST (r = −0.459, p = 0.036) and ODI during

Summary

Introduction

Atrial fibrillation (AF) is one of the most common heart diseases. It is a major healthcare problem due to its increasing prevalence and associated thromboembolism, heart failure, frequent hospitalizations, and mortality [1,2]. OSAS has been reported to be related to hypertension, and it increases the risk of AF, heart failure, myocardial infarction, stroke, and even mortality [4,5,6,7,8]. There are some reports on the relationship between AF and OSAS that show the incidence of AF is associated with OSAS severity, that AF patients with OSAS have a worse prognosis (a higher AF recurrence rate) whether receiving medication or ablation therapy [6,7] and that the treatment strategy (e.g., nasal continuous positive airway pressure) for OSAS may decrease the number of AF attacks [11]

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