Role of S100A8 in atrial fibrillation associated with obstructive sleep ap-nea in dogs
10.3969/j.issn.1000-4718.2025.07.010
- VernacularTitle:S100A8在阻塞性睡眠呼吸暂停诱发犬心房颤动模型中的作用
- Author:
XIAOKERETI JIASUOER
1
;
Xinyuan MA
;
Wenqi WANG
;
Siwen LIU
;
YIMITI ADILA
;
Ruixiao LEI
;
Ling ZHANG
Author Information
1. 新疆医科大学第一附属医院心脏起搏电生理科,新疆 乌鲁木齐 830054;新疆医科大学第一附属医院新疆心电生理与心脏重塑重点实验室,新疆 乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
obstructive sleep apnea;
atrial fibrillation;
proteomics;
fibrosis;
inflammation;
S100 calcium-binding protein A8
- From:
Chinese Journal of Pathophysiology
2025;41(7):1334-1344
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.
