{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T02:18:05Z","timestamp":1787797085291,"version":"build-2784847793"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":70,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100019065","name":"Tianjin Science and Technology Plan Project","doi-asserted-by":"crossref","award":["22JCYBJC00580"],"award-info":[{"award-number":["22JCYBJC00580"]}],"id":[{"id":"10.13039\/501100019065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cardiothorac Surg"],"DOI":"10.1186\/s13019-026-04369-2","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:13:36Z","timestamp":1781756016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and validation of five hypoxia- and immune-related hub targets in atrial fibrillation"],"prefix":"10.1186","volume":"21","author":[{"given":"Jinri","family":"Weng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qile","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"issue":"11","key":"4369_CR1","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrcardio.2014.118","volume":"11","author":"F Rahman","year":"2014","unstructured":"Rahman F, Kwan GF, Benjamin EJ. Global epidemiology of atrial fibrillation. Nat Rev Cardiol. 2014;11(11):639\u201354. https:\/\/doi.org\/10.1038\/nrcardio.2014.118.","journal-title":"Nat Rev Cardiol"},{"issue":"25","key":"4369_CR2","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","volume":"76","author":"GA Roth","year":"2020","unstructured":"Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982\u20133021. https:\/\/doi.org\/10.1016\/j.jacc.2020.11.010.","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"4369_CR3","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1002\/cphy.c140047","volume":"5","author":"J Pellman","year":"2015","unstructured":"Pellman J, Sheikh F. Atrial fibrillation: mechanisms, therapeutics, and future directions. Compr Physiol. 2015;5(2):649\u201365. https:\/\/doi.org\/10.1002\/cphy.c140047.","journal-title":"Compr Physiol"},{"issue":"5","key":"4369_CR4","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","volume":"42","author":"G Hindricks","year":"2021","unstructured":"Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42(5):373\u2013498. https:\/\/doi.org\/10.1093\/eurheartj\/ehaa612.","journal-title":"Eur Heart J"},{"issue":"1","key":"4369_CR5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/europace\/euac143","volume":"25","author":"E Charitakis","year":"2023","unstructured":"Charitakis E, Dragioti E, Stratinaki M, Korela D, Tzeis S, Almroth H, et al. Predictors of recurrence after catheter ablation and electrical cardioversion of atrial fibrillation: an umbrella review of meta-analyses. Europace. 2023;25(1):40\u20138. https:\/\/doi.org\/10.1093\/europace\/euac143.","journal-title":"Europace"},{"issue":"4","key":"4369_CR6","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1097\/HCO.0000000000000307","volume":"31","author":"M Labedi","year":"2016","unstructured":"Labedi M, Marrouche N. Invasive treatment of atrial fibrillation. Curr Opin Cardiol. 2016;31(4):366\u201373. https:\/\/doi.org\/10.1097\/HCO.0000000000000307.","journal-title":"Curr Opin Cardiol"},{"issue":"3","key":"4369_CR7","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s00210-009-0487-8","volume":"381","author":"U Ravens","year":"2010","unstructured":"Ravens U. Novel pharmacological approaches for antiarrhythmic therapy. Naunyn Schmiedebergs Arch Pharmacol. 2010;381(3):187\u201393. https:\/\/doi.org\/10.1007\/s00210-009-0487-8.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"4369_CR8","doi-asserted-by":"publisher","first-page":"103588","DOI":"10.1016\/j.resp.2020.103588","volume":"285","author":"S Bagali","year":"2021","unstructured":"Bagali S, Das KK. Hypoxia and its preconditioning on cardiac and vascular remodelling in experimental animals. Respir Physiol Neurobiol. 2021;285:103588. https:\/\/doi.org\/10.1016\/j.resp.2020.103588.","journal-title":"Respir Physiol Neurobiol"},{"issue":"2","key":"4369_CR9","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.carpath.2008.11.001","volume":"19","author":"F Gramley","year":"2010","unstructured":"Gramley F, Lorenzen J, Jedamzik B, Gatter K, Koellensperger E, Munzel T, et al. Atrial fibrillation is associated with cardiac hypoxia. Cardiovasc Pathol. 2010;19(2):102\u201311. https:\/\/doi.org\/10.1016\/j.carpath.2008.11.001.","journal-title":"Cardiovasc Pathol"},{"issue":"1","key":"4369_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.18632\/aging.204470","volume":"15","author":"Y Tian","year":"2023","unstructured":"Tian Y, Liu S, Zhang Y, Yang J, Guo P, Zhang H, et al. Immune infiltration and immunophenotyping in atrial fibrillation. Aging. 2023;15(1):213\u201329. https:\/\/doi.org\/10.18632\/aging.204470.","journal-title":"Aging"},{"issue":"1","key":"4369_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/joa3.12473","volume":"37","author":"N Nso","year":"2021","unstructured":"Nso N, Bookani KR, Metzl M, Radparvar F. Role of inflammation in atrial fibrillation: A comprehensive review of current knowledge. J Arrhythm. 2021;37(1):1\u201310. https:\/\/doi.org\/10.1002\/joa3.12473.","journal-title":"J Arrhythm"},{"issue":"4","key":"4369_CR12","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.immuni.2014.09.008","volume":"41","author":"A Palazon","year":"2014","unstructured":"Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity. 2014;41(4):518\u201328. https:\/\/doi.org\/10.1016\/j.immuni.2014.09.008.","journal-title":"Immunity"},{"key":"4369_CR13","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.yjmcc.2018.09.007","volume":"123","author":"Y Liu","year":"2018","unstructured":"Liu Y, Shi Q, Ma Y, Liu Q. The role of immune cells in atrial fibrillation. J Mol Cell Cardiol. 2018;123:198\u2013208. https:\/\/doi.org\/10.1016\/j.yjmcc.2018.09.007.","journal-title":"J Mol Cell Cardiol"},{"issue":"7","key":"4369_CR14","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. https:\/\/doi.org\/10.1093\/nar\/gkv007.","journal-title":"Nucleic Acids Res"},{"key":"4369_CR15","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","volume":"9","author":"P Langfelder","year":"2008","unstructured":"Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. https:\/\/doi.org\/10.1186\/1471-2105-9-559.","journal-title":"BMC Bioinformatics"},{"issue":"D1","key":"4369_CR16","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607\u201313. https:\/\/doi.org\/10.1093\/nar\/gky1131.","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"4369_CR17","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498\u2013504. https:\/\/doi.org\/10.1101\/gr.1239303.","journal-title":"Genome Res"},{"issue":"5","key":"4369_CR18","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284\u20137. https:\/\/doi.org\/10.1089\/omi.2011.0118.","journal-title":"OMICS"},{"issue":"5","key":"4369_CR19","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453\u20137. https:\/\/doi.org\/10.1038\/nmeth.3337.","journal-title":"Nat Methods"},{"issue":"W1","key":"4369_CR20","doi-asserted-by":"publisher","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","volume":"48","author":"T Li","year":"2020","unstructured":"Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48(W1):W509\u201314. https:\/\/doi.org\/10.1093\/nar\/gkaa407.","journal-title":"Nucleic Acids Res"},{"key":"4369_CR21","doi-asserted-by":"publisher","first-page":"1224892","DOI":"10.3389\/fimmu.2023.1224892","volume":"14","author":"D Song","year":"2023","unstructured":"Song D, Lian Y, Zhang L. The potential of activator protein 1 (AP-1) in cancer targeted therapy. Front Immunol. 2023;14:1224892. https:\/\/doi.org\/10.3389\/fimmu.2023.1224892.","journal-title":"Front Immunol"},{"issue":"5","key":"4369_CR22","doi-asserted-by":"publisher","first-page":"E131","DOI":"10.1038\/ncb0502-e131","volume":"4","author":"E Shaulian","year":"2002","unstructured":"Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002;4(5):E131\u20136. https:\/\/doi.org\/10.1038\/ncb0502-e131.","journal-title":"Nat Cell Biol"},{"key":"4369_CR23","doi-asserted-by":"publisher","first-page":"8323","DOI":"10.1038\/ncomms9323","volume":"6","author":"Z Chen","year":"2015","unstructured":"Chen Z, Lan X, Wu D, Sunkel B, Ye Z, Huang J, et al. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun. 2015;6:8323. https:\/\/doi.org\/10.1038\/ncomms9323.","journal-title":"Nat Commun"},{"issue":"7414","key":"4369_CR24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","volume":"489","author":"EP Consortium","year":"2012","unstructured":"Consortium EP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57\u201374. https:\/\/doi.org\/10.1038\/nature11247.","journal-title":"Nature"},{"issue":"D1","key":"4369_CR25","doi-asserted-by":"publisher","first-page":"D794","DOI":"10.1093\/nar\/gkx1081","volume":"46","author":"CA Davis","year":"2018","unstructured":"Davis CA, Hitz BC, Sloan CA, Chan ET, Davidson JM, Gabdank I, et al. The Encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res. 2018;46(D1):D794\u2013801. https:\/\/doi.org\/10.1093\/nar\/gkx1081.","journal-title":"Nucleic Acids Res"},{"issue":"7527","key":"4369_CR26","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/nature13986","volume":"515","author":"BD Pope","year":"2014","unstructured":"Pope BD, Ryba T, Dileep V, Yue F, Wu W, Denas O, et al. Topologically associating domains are stable units of replication-timing regulation. Nature. 2014;515(7527):402\u20135. https:\/\/doi.org\/10.1038\/nature13986.","journal-title":"Nature"},{"issue":"11","key":"4369_CR27","doi-asserted-by":"publisher","first-page":"e012199","DOI":"10.1161\/CIRCEP.123.012199","volume":"16","author":"TW Dorey","year":"2023","unstructured":"Dorey TW, Liu Y, Jansen HJ, Bohne LJ, Mackasey M, Atkinson L, et al. Natriuretic Peptide Receptor B Protects Against Atrial Fibrillation by Controlling Atrial cAMP Via Phosphodiesterase 2. Circ Arrhythm Electrophysiol. 2023;16(11):e012199. https:\/\/doi.org\/10.1161\/CIRCEP.123.012199.","journal-title":"Circ Arrhythm Electrophysiol"},{"issue":"27","key":"4369_CR28","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1093\/eurheartj\/ehad086","volume":"44","author":"N Grammatika Pavlidou","year":"2023","unstructured":"Grammatika Pavlidou N, Dobrev S, Beneke K, Reinhardt F, Pecha S, Jacquet E, et al. Phosphodiesterase 8 governs cAMP\/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism. Eur Heart J. 2023;44(27):2483\u201394. https:\/\/doi.org\/10.1093\/eurheartj\/ehad086.","journal-title":"Eur Heart J"},{"issue":"2","key":"4369_CR29","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1177\/1747493019897870","volume":"16","author":"G Lippi","year":"2021","unstructured":"Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. Int J Stroke. 2021;16(2):217\u201321. https:\/\/doi.org\/10.1177\/1747493019897870.","journal-title":"Int J Stroke"},{"issue":"1","key":"4369_CR30","doi-asserted-by":"publisher","first-page":"16678","DOI":"10.1038\/s41598-017-16938-6","volume":"7","author":"A Sultan","year":"2017","unstructured":"Sultan A, Luker J, Andresen D, Kuck KH, Hoffmann E, Brachmann J, et al. Predictors of Atrial Fibrillation Recurrence after Catheter Ablation: Data from the German Ablation Registry. Sci Rep. 2017;7(1):16678. https:\/\/doi.org\/10.1038\/s41598-017-16938-6.","journal-title":"Sci Rep"},{"issue":"23","key":"4369_CR31","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1161\/CIRCULATIONAHA.110.946806","volume":"122","author":"F Ouyang","year":"2010","unstructured":"Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, et al. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation. 2010;122(23):2368\u201377. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.110.946806.","journal-title":"Circulation"},{"issue":"1","key":"4369_CR32","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41537-024-00469-x","volume":"10","author":"Y Dong","year":"2024","unstructured":"Dong Y, Zhu M, Li Y, Liu N, Wang X, Yang B, et al. Association of cytokines levels, psychopathology and cognition among CR-TRS patients with metabolic syndrome. Schizophrenia (Heidelb). 2024;10(1):47. https:\/\/doi.org\/10.1038\/s41537-024-00469-x.","journal-title":"Schizophrenia (Heidelb)"},{"issue":"5","key":"4369_CR33","doi-asserted-by":"publisher","first-page":"438","DOI":"10.14348\/molcells.2019.2275","volume":"43","author":"Y Chen","year":"2020","unstructured":"Chen Y, Chang G, Chen X, Li Y, Li H, Cheng D, et al. IL-6-miR-210 Suppresses Regulatory T Cell Function and Promotes Atrial Fibrosis by Targeting Foxp3. Mol Cells. 2020;43(5):438\u201347. https:\/\/doi.org\/10.14348\/molcells.2019.2275.","journal-title":"Mol Cells"},{"issue":"11","key":"4369_CR34","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1016\/j.hrthm.2018.06.025","volume":"15","author":"I Abe","year":"2018","unstructured":"Abe I, Teshima Y, Kondo H, Kaku H, Kira S, Ikebe Y, et al. Association of fibrotic remodeling and cytokines\/chemokines content in epicardial adipose tissue with atrial myocardial fibrosis in patients with atrial fibrillation. Heart Rhythm. 2018;15(11):1717\u201327. https:\/\/doi.org\/10.1016\/j.hrthm.2018.06.025.","journal-title":"Heart Rhythm"},{"issue":"4","key":"4369_CR35","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/0891-5849(96)00160-8","volume":"21","author":"DR Crawford","year":"1996","unstructured":"Crawford DR, Leahy KP, Wang Y, Schools GP, Kochheiser JC, Davies KJ. Oxidative stress induces the levels of a MafG homolog in hamster HA-1 cells. Free Radic Biol Med. 1996;21(4):521\u20135. https:\/\/doi.org\/10.1016\/0891-5849(96)00160-8.","journal-title":"Free Radic Biol Med"},{"key":"4369_CR36","doi-asserted-by":"publisher","DOI":"10.2174\/0929867330666230209100059","author":"Z Pi","year":"2023","unstructured":"Pi Z, Qiu X, Liu J, Shi Y, Zeng Z, Xiao R. Activating Protein-1 (AP-1): A Promising Target for the Treatment of Fibrotic Diseases. Curr Med Chem. 2023. https:\/\/doi.org\/10.2174\/0929867330666230209100059.","journal-title":"Curr Med Chem"},{"key":"4369_CR37","doi-asserted-by":"publisher","unstructured":"Seidenberg J, Stellato M, Hukara A, Ludewig B, Klingel K, Distler O, et al. The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis. Int J Mol Sci. 2021;22(4). https:\/\/doi.org\/10.3390\/ijms22041861.","DOI":"10.3390\/ijms22041861"},{"issue":"1","key":"4369_CR38","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41392-020-0114-1","volume":"5","author":"X Palomer","year":"2020","unstructured":"Palomer X, Roman-Azcona MS, Pizarro-Delgado J, Planavila A, Villarroya F, Valenzuela-Alcaraz B, et al. SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation. Signal Transduct Target therapy. 2020;5(1):14. https:\/\/doi.org\/10.1038\/s41392-020-0114-1.","journal-title":"Signal Transduct Target therapy"},{"issue":"5","key":"4369_CR39","doi-asserted-by":"publisher","first-page":"e35144","DOI":"10.1371\/journal.pone.0035144","volume":"7","author":"F Ma","year":"2012","unstructured":"Ma F, Li Y, Jia L, Han Y, Cheng J, Li H, et al. Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF beta\/Smad activation and cardiac fibrosis induced by angiotensin II. PLoS ONE. 2012;7(5):e35144. https:\/\/doi.org\/10.1371\/journal.pone.0035144.","journal-title":"PLoS ONE"},{"issue":"11","key":"4369_CR40","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1007\/s00109-006-0090-0","volume":"84","author":"D Schroder","year":"2006","unstructured":"Schroder D, Heger J, Piper HM, Euler G. Angiotensin II stimulates apoptosis via TGF-beta1 signaling in ventricular cardiomyocytes of rat. J Mol Med (Berl). 2006;84(11):975\u201383. https:\/\/doi.org\/10.1007\/s00109-006-0090-0.","journal-title":"J Mol Med (Berl)"},{"issue":"17","key":"4369_CR41","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1161\/CIRCULATIONAHA.111.067306","volume":"125","author":"N Voigt","year":"2012","unstructured":"Voigt N, Li N, Wang Q, Wang W, Trafford AW, Abu-Taha I, et al. Enhanced sarcoplasmic reticulum Ca2\u2009+\u2009leak and increased Na+-Ca2\u2009+\u2009exchanger function underlie delayed afterdepolarizations in patients with chronic atrial fibrillation. Circulation. 2012;125(17):2059\u201370. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.111.067306.","journal-title":"Circulation"},{"issue":"6","key":"4369_CR42","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1093\/eurheartj\/ehq464","volume":"32","author":"A Llach","year":"2011","unstructured":"Llach A, Molina CE, Prat-Vidal C, Fernandes J, Casado V, Ciruela F, et al. Abnormal calcium handling in atrial fibrillation is linked to up-regulation of adenosine A2A receptors. Eur Heart J. 2011;32(6):721\u20139. https:\/\/doi.org\/10.1093\/eurheartj\/ehq464.","journal-title":"Eur Heart J"},{"issue":"9","key":"4369_CR43","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1161\/CIRCRESAHA.114.303772","volume":"114","author":"PS Chen","year":"2014","unstructured":"Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res. 2014;114(9):1500\u201315. https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.303772.","journal-title":"Circ Res"},{"issue":"3","key":"4369_CR44","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1113\/jphysiol.2011.223842","volume":"590","author":"T Ikeda","year":"2012","unstructured":"Ikeda T, Murai H, Kaneko S, Usui S, Kobayashi D, Nakano M, et al. Augmented single-unit muscle sympathetic nerve activity in heart failure with chronic atrial fibrillation. J Physiol. 2012;590(3):509\u201318. https:\/\/doi.org\/10.1113\/jphysiol.2011.223842.","journal-title":"J Physiol"},{"issue":"3","key":"4369_CR45","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00210-009-0474-0","volume":"381","author":"AJ Workman","year":"2010","unstructured":"Workman AJ. Cardiac adrenergic control and atrial fibrillation. Naunyn Schmiedebergs Arch Pharmacol. 2010;381(3):235\u201349. https:\/\/doi.org\/10.1007\/s00210-009-0474-0.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"1","key":"4369_CR46","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s12012-024-09937-3","volume":"25","author":"L Wu","year":"2025","unstructured":"Wu L, Yang B, Sun Y, Fan G, Ma L, Ma Y, et al. Isoprenaline Inhibits Histone Demethylase LSD1 to Induce Cardiac Hypertrophy. Cardiovasc Toxicol. 2025;25(1):34\u201347. https:\/\/doi.org\/10.1007\/s12012-024-09937-3.","journal-title":"Cardiovasc Toxicol"},{"key":"4369_CR47","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1146\/annurev-physiol-060121-041653","volume":"84","author":"A Papa","year":"2022","unstructured":"Papa A, Kushner J, Marx SO. Adrenergic Regulation of Calcium Channels in the Heart. Annu Rev Physiol. 2022;84:285\u2013306. https:\/\/doi.org\/10.1146\/annurev-physiol-060121-041653.","journal-title":"Annu Rev Physiol"},{"issue":"5","key":"4369_CR48","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1161\/CIRCRESAHA.113.301781","volume":"113","author":"S Weiss","year":"2013","unstructured":"Weiss S, Oz S, Benmocha A, Dascal N. Regulation of cardiac L-type Ca(2)(+) channel CaV1.2 via the beta-adrenergic-cAMP-protein kinase A pathway: old dogmas, advances, and new uncertainties. Circ Res. 2013;113(5):617\u201331. https:\/\/doi.org\/10.1161\/CIRCRESAHA.113.301781.","journal-title":"Circ Res"},{"issue":"9","key":"4369_CR49","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1161\/CIRCRESAHA.114.302226","volume":"114","author":"J Heijman","year":"2014","unstructured":"Heijman J, Voigt N, Nattel S, Dobrev D. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ Res. 2014;114(9):1483\u201399. https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.302226.","journal-title":"Circ Res"},{"issue":"11","key":"4369_CR50","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1161\/01.CIR.0000141296.59876.87","volume":"110","author":"L Hove-Madsen","year":"2004","unstructured":"Hove-Madsen L, Llach A, Bayes-Genis A, Roura S, Rodriguez Font E, Aris A, et al. Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes. Circulation. 2004;110(11):1358\u201363. https:\/\/doi.org\/10.1161\/01.CIR.0000141296.59876.87.","journal-title":"Circulation"},{"issue":"4","key":"4369_CR51","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1161\/CIRCRESAHA.120.318409","volume":"128","author":"J Yan","year":"2021","unstructured":"Yan J, Bare DJ, DeSantiago J, Zhao W, Mei Y, Chen Z, et al. JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca(2+)](SR) Leak-Load Relationship. Circ Res. 2021;128(4):455\u201370. https:\/\/doi.org\/10.1161\/CIRCRESAHA.120.318409.","journal-title":"Circ Res"},{"issue":"6","key":"4369_CR52","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1161\/CIRCRESAHA.117.312536","volume":"122","author":"J Yan","year":"2018","unstructured":"Yan J, Zhao W, Thomson JK, Gao X, DeMarco DM, Carrillo E, et al. Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis. Circ Res. 2018;122(6):821\u201335. https:\/\/doi.org\/10.1161\/CIRCRESAHA.117.312536.","journal-title":"Circ Res"},{"key":"4369_CR53","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.yjmcc.2017.11.006","volume":"114","author":"J Yan","year":"2018","unstructured":"Yan J, Thomson JK, Zhao W, Wu X, Gao X, DeMarco D, et al. The stress kinase JNK regulates gap junction Cx43 gene expression and promotes atrial fibrillation in the aged heart. J Mol Cell Cardiol. 2018;114:105\u201315. https:\/\/doi.org\/10.1016\/j.yjmcc.2017.11.006.","journal-title":"J Mol Cell Cardiol"},{"issue":"19","key":"4369_CR54","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1016\/j.lfs.2007.02.029","volume":"80","author":"SH Lee","year":"2007","unstructured":"Lee SH, Chen YC, Chen YJ, Chang SL, Tai CT, Wongcharoen W, et al. Tumor necrosis factor-alpha alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes. Life Sci. 2007;80(19):1806\u201315. https:\/\/doi.org\/10.1016\/j.lfs.2007.02.029.","journal-title":"Life Sci"},{"issue":"6","key":"4369_CR55","doi-asserted-by":"publisher","first-page":"C1420","DOI":"10.1152\/ajpcell.00534.2002","volume":"285","author":"JM Pei","year":"2003","unstructured":"Pei JM, Kravtsov GM, Wu S, Das R, Fung ML, Wong TM. Calcium homeostasis in rat cardiomyocytes during chronic hypoxia: a time course study. Am J Physiol Cell Physiol. 2003;285(6):C1420\u20138. https:\/\/doi.org\/10.1152\/ajpcell.00534.2002.","journal-title":"Am J Physiol Cell Physiol"},{"issue":"2","key":"4369_CR56","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1093\/toxsci\/kfad094","volume":"196","author":"D Filipovic","year":"2023","unstructured":"Filipovic D, Qi W, Kana O, Marri D, LeCluyse EL, Andersen ME, et al. Interpretable predictive models of genome-wide aryl hydrocarbon receptor-DNA binding reveal tissue-specific binding determinants. Toxicol Sci. 2023;196(2):170\u201386. https:\/\/doi.org\/10.1093\/toxsci\/kfad094.","journal-title":"Toxicol Sci"},{"issue":"1","key":"4369_CR57","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13059-020-02218-6","volume":"22","author":"D Srivastava","year":"2021","unstructured":"Srivastava D, Aydin B, Mazzoni EO, Mahony S. An interpretable bimodal neural network characterizes the sequence and preexisting chromatin predictors of induced transcription factor binding. Genome Biol. 2021;22(1):20. https:\/\/doi.org\/10.1186\/s13059-020-02218-6.","journal-title":"Genome Biol"}],"container-title":["Journal of Cardiothoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13019-026-04369-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13019-026-04369-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13019-026-04369-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:42:24Z","timestamp":1787794944000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13019-026-04369-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4369"],"URL":"https:\/\/doi.org\/10.1186\/s13019-026-04369-2","relation":{},"ISSN":["1749-8090"],"issn-type":[{"value":"1749-8090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]},"assertion":[{"value":"24 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Ethics Committee of the Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University (2026018) and written informed consent was obtained from all participants.","order":1,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"640"}}