Identification of a Novel Target Implicated in Chronic Obstructive Sleep Apnea-Related Atrial Fibrillation by Integrative Analysis of Transcriptome and Proteome

Jun Shen,1,2,* Junqing Liang,1,2,* Manzeremu Rejiepu,1,2,* Ping Yuan,3 Jie Xiang,1,2 Yankai Guo,1,2 Jiasuoer Xiaokereti,1,2 Ling Zhang,1,2 Baopeng Tang1,2 1Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Zhang, Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel/Fax +86 18690280833, Email ydzhangling@126.com Baopeng Tang, Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang, 830000, People’s Republic of China, Tel/Fax +86 13477301883, Email tangbaopeng1111@163.comObjective: This study aimed to identify a newly identified target involved in atrial fibrillation (AF) linked to chronic obstructive sleep apnea (COSA) through an integrative analysis of transcriptome and proteome.Methods: Fifteen beagle canines were randomly assigned to three groups: control (CON), obstructive sleep apnea (OSA), and OSA with superior left ganglionated plexi ablation (OSA+GP). A COSA model was established by intermittently obstructing the endotracheal cannula during exhalation for 12 weeks. Left parasternal thoracotomy through the fourth intercostal space allowed for superior left ganglionated plexi (SLGP) ablation. In vivo open-chest electrophysiological programmed stimulation was performed to assess AF inducibility. Histological, transcriptomic, and proteomic analyses were conducted on atrial samples.Results: After 12 weeks, the OSA group exhibited increased AF inducibility and longer AF durations compared to the CON group. Integrated transcriptomic and proteomic analyses identified 2422 differentially expressed genes (DEGs) and 1194 differentially expressed proteins (DEPs) between OSA and CON groups, as well as between OSA+GP and OSA groups (1850 DEGs and 1418 DEPs). The analysis revealed that differentially regulated DEGs were primarily enriched in mitochondrial biological processes in the CON-vs.-OSA and OSA-vs.-GP comparisons. Notably, the key regulatory molecule GSTZ1 was activated in OSA and inhibited by GP ablation.Conclusion: These findings suggest that GSTZ1 may play a pivotal role in mitochondrial damage, triggering AF substrate formation, and increasing susceptibility to AF in the context of COSA.Keywords: atrial fibrillation, obstructive sleep apnea, transcriptome, proteomic, ganglionated plexi ablation