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

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

doi:10.3390/biomedicines9101463

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

Biomedicines. 2021 Oct 13;9(10):1463. doi: 10.3390/biomedicines9101463.

Authors

Yung-Lung Chen^{1

2

3}, Yung-Che Chen^{3

4}, Ya-Ting Chang⁵, Hui-Ting Wang⁶, Wen-Hao Liu^{1

3}, Shaur-Zheng Chong^{1

3}, Pei-Ting Lin^{1

3}, Po-Yuan Hsu^{3

4}, Mao-Chang Su^{3

4}, Meng-Chih Lin^{3

4}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
² Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
³ School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁴ Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
⁵ Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
⁶ Emergency Department, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.

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.

Keywords: GJA1; atrial fibrillation; left atrial remodeling; nocturnal oxygen desaturation; obstructive sleep apnea syndrome; sleep efficiency.

Abstract

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