{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:33:47Z","timestamp":1789558427441,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022232","name":"Gaofeng Clinical Medicine","doi-asserted-by":"publisher","award":["20161404"],"award-info":[{"award-number":["20161404"]}],"id":[{"id":"10.13039\/501100022232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016983","name":"Clinical Research Plan for Shanghai Hospital Development Center","doi-asserted-by":"publisher","award":["SHD2020CR4096"],"award-info":[{"award-number":["SHD2020CR4096"]}],"id":[{"id":"10.13039\/501100016983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100329"],"award-info":[{"award-number":["82100329"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P &amp;lt; 0.0001) and the left atria (P &amp;lt; 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P &amp;lt; 0.05) and postprocedural recurrence (hazard ratio = 22.955, P &amp;lt; 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-\u03b3, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvae222","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T23:19:30Z","timestamp":1728343170000},"page":"97-112","source":"Crossref","is-referenced-by-count":18,"title":["Senescent CD8+ T cells: a novel risk factor in atrial fibrillation"],"prefix":"10.1093","volume":"121","author":[{"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimo","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taojie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyou","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]},{"name":"Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]},{"name":"Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-072X","authenticated-orcid":false,"given":"Qi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Ruijin Road Number Two, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"2025041515290582700_cvae222-B1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/CIRCULATIONAHA.113.005119","article-title":"Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study","volume":"129","author":"Chugh","year":"2014","journal-title":"Circulation"},{"key":"2025041515290582700_cvae222-B2","doi-asserted-by":"crossref","first-page":"e004549","DOI":"10.1161\/JAHA.112.004549","article-title":"Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis","volume":"2","author":"Ganesan","year":"2013","journal-title":"J Am Heart Assoc Cardiovasc Cerebrovasc Dis"},{"key":"2025041515290582700_cvae222-B3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ahj.2007.09.006","article-title":"Interleukin-6 and atrial fibrillation in patients with coronary artery disease: data from the Heart and Soul study","volume":"155","author":"Marcus","year":"2008","journal-title":"Am Heart J"},{"key":"2025041515290582700_cvae222-B4","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1093\/europace\/eun111","article-title":"Source of inflammatory markers in patients with atrial fibrillation","volume":"10","author":"Liuba","year":"2008","journal-title":"Eurospace"},{"key":"2025041515290582700_cvae222-B5","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1161\/CIRCEP.111.965996","article-title":"Electrophysiological correlation and prognostic impact of heat shock protein 27 in atrial fibrillation","volume":"5","author":"Hu","year":"2012","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2025041515290582700_cvae222-B6","doi-asserted-by":"crossref","first-page":"927221","DOI":"10.3389\/fphys.2022.927221","article-title":"Immune remodeling and atrial fibrillation","volume":"13","author":"Yao","year":"2022","journal-title":"Front Physiol"},{"key":"2025041515290582700_cvae222-B7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"2025041515290582700_cvae222-B8","doi-asserted-by":"crossref","first-page":"175754","DOI":"10.1016\/j.ejphar.2023.175754","article-title":"Sacubitril\/valsartan reduces susceptibility to atrial fibrillation by improving atrial remodeling in spontaneously hypertensive rats","volume":"952","author":"Li","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"2025041515290582700_cvae222-B9","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1101\/gad.343129.120","article-title":"Senescence and the SASP: many therapeutic avenues","volume":"34","author":"Birch","year":"2020","journal-title":"Genes Dev"},{"key":"2025041515290582700_cvae222-B10","doi-asserted-by":"crossref","first-page":"e301","DOI":"10.1371\/journal.pbio.0060301","article-title":"Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor","volume":"6","author":"Copp\u00e9","year":"2008","journal-title":"PLOS Biol"},{"key":"2025041515290582700_cvae222-B11","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41569-020-0394-8","article-title":"Intracellular calcium leak: a unifying mechanism and therapeutic target for heart failure and atrial fibrillation","volume":"17","author":"Dridi","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2025041515290582700_cvae222-B12","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1161\/CIRCRESAHA.120.316710","article-title":"Atrial myocyte NLRP3\/CaMKII nexus forms a substrate for postoperative atrial fibrillation","volume":"127","author":"Heijman","year":"2020","journal-title":"Circ Res"},{"key":"2025041515290582700_cvae222-B13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1161\/CIRCEP.107.754564","article-title":"Atrial remodeling and atrial fibrillation: mechanisms and implications","volume":"1","author":"Nattel","year":"2008","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"2025041515290582700_cvae222-B14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.hrthm.2022.10.012","article-title":"Immune cell subpopulations as risk factors for atrial fibrillation: the Cardiovascular Health Study and Multi-Ethnic Study of Atherosclerosis","volume":"20","author":"Floyd","year":"2023","journal-title":"Heart Rhythm"},{"key":"2025041515290582700_cvae222-B15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1126\/science.abq3061","article-title":"Recruited macrophages elicit atrial fibrillation","volume":"381","author":"Hulsmans","year":"2023","journal-title":"Science"},{"key":"2025041515290582700_cvae222-B16","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0140-6736(09)60443-8","article-title":"Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study","volume":"373","author":"Schnabel","year":"2009","journal-title":"Lancet Lond Engl"},{"key":"2025041515290582700_cvae222-B17","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","article-title":"Mechanisms underlying T cell ageing","volume":"19","author":"Goronzy","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"2025041515290582700_cvae222-B18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/cvr\/cvaa032","article-title":"T-cell senescence accelerates angiotensin II-induced target organ damage","volume":"117","author":"Pan","year":"2021","journal-title":"Cardiovasc Res"},{"key":"2025041515290582700_cvae222-B19","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1038\/s41467-022-31135-4","article-title":"T cell cholesterol efflux suppresses apoptosis and senescence and increases atherosclerosis in middle aged mice","volume":"13","author":"Bazioti","year":"2022","journal-title":"Nat Commun"},{"key":"2025041515290582700_cvae222-B20","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/cmi.2014.74","article-title":"Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction","volume":"12","author":"Tae Yu","year":"2015","journal-title":"Cell Mol Immunol"},{"key":"2025041515290582700_cvae222-B21","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1182\/blood-2002-07-2103","article-title":"Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells","volume":"101","author":"Brenchley","year":"2003","journal-title":"Blood"},{"key":"2025041515290582700_cvae222-B22","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1172\/JCI75051","article-title":"P38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells","volume":"124","author":"Henson","year":"2014","journal-title":"J Clin Invest"},{"key":"2025041515290582700_cvae222-B23","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/imcb.12169","article-title":"CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome","volume":"96","author":"Cura Daball","year":"2018","journal-title":"Immunol Cell Biol"},{"key":"2025041515290582700_cvae222-B24","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.1172\/JCI70355","article-title":"P53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes","volume":"123","author":"Mondal","year":"2013","journal-title":"J Clin Invest"},{"key":"2025041515290582700_cvae222-B25","doi-asserted-by":"crossref","first-page":"e13262","DOI":"10.1111\/acel.13262","article-title":"How age and infection history shape the antigen-specific CD8+ T-cell repertoire: implications for vaccination strategies in older adults","volume":"19","author":"Lanfermeijer","year":"2020","journal-title":"Aging Cell"},{"key":"2025041515290582700_cvae222-B26","doi-asserted-by":"crossref","first-page":"e13316","DOI":"10.1111\/acel.13316","article-title":"Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells","volume":"20","author":"Zhou","year":"2021","journal-title":"Aging Cell"},{"key":"2025041515290582700_cvae222-B27","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1161\/01.CIR.0000141296.59876.87","article-title":"Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes","volume":"110","author":"Hove-Madsen","year":"2004","journal-title":"Circulation"},{"key":"2025041515290582700_cvae222-B28","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.hrthm.2019.01.013","article-title":"Calcium\/calmodulin-dependent protein kinase II causes atrial structural remodeling associated with atrial fibrillation and heart failure","volume":"16","author":"Liu","year":"2019","journal-title":"Heart Rhythm"},{"key":"2025041515290582700_cvae222-B29","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/CIRCRESAHA.112.273342","article-title":"Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia","volume":"111","author":"Shan","year":"2012","journal-title":"Circ Res"},{"key":"2025041515290582700_cvae222-B30","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1161\/CIRCRESAHA.110.223586","article-title":"Alternans arrhythmias: from cell to heart","volume":"108","author":"Weiss","year":"2011","journal-title":"Circ Res"},{"key":"2025041515290582700_cvae222-B31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.freeradbiomed.2021.05.003","article-title":"Senolytics and senomorphics: natural and synthetic therapeutics in the treatment of aging and chronic diseases","volume":"171","author":"Lagoumtzi","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"2025041515290582700_cvae222-B32","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/FJC.0000000000000878","article-title":"Senolytic agent navitoclax inhibits angiotensin II-induced heart failure in mice","volume":"76","author":"Jia","year":"2020","journal-title":"J Cardiovasc Pharmacol"},{"key":"2025041515290582700_cvae222-B33","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: from mechanisms to therapeutic opportunities","volume":"22","author":"Di Micco","year":"2021","journal-title":"Nat Rev Mol Cell Biol"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvae222\/60087728\/cvae222.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/121\/1\/97\/60087728\/cvae222.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/121\/1\/97\/60087728\/cvae222.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T11:29:16Z","timestamp":1744716556000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/121\/1\/97\/7816130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,10,9]]},"published-print":{"date-parts":[[2025,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvae222","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,10,9]]}}}