{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:49Z","timestamp":1792785889335,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2023AFB140"],"award-info":[{"award-number":["2023AFB140"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Project of Hubei Key Laboratory","award":["2023KFZZ025"],"award-info":[{"award-number":["2023KFZZ025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ventricular arrhythmias (VAs), which can lead to sudden cardiac death, are the primary cause of mortality in patients with heart failure (HF). However, the precise mechanisms underlying these arrhythmias are not well understood. Recent studies have implicated tumour necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in pathological cardiac hypertrophy. Nevertheless, its role in isoproterenol (ISO)-associated VAs remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We overexpressed TNIP3 in the myocardium using an adeno-associated virus 9 system, administered via tail vein injection. C57BL\/6 mice received daily subcutaneous injections of ISO for two consecutive weeks to establish an HF model. We performed histopathology and electrophysiological studies to assess ventricular structural remodelling, electrical remodelling, and susceptibility to VAs. Additionally, RNA sequencing (RNA-Seq) and western blot analysis were conducted to elucidate the underlying mechanisms. The expression of TNIP3 was up-regulated following ISO treatment. TNIP3 overexpression significantly reversed ISO-induced cardiac dysfunction, fibrosis, electrical remodelling, and VAs susceptibility. Accordingly, RNA-Seq identifies that the inflammatory response takes an important role in ISO-induced Vas, and TNIP3 overexpression could alleviate ISO-induced cardiac proinflammatory response by promoting M1 to M2 macrophage polarization. Mechanistically, PI3K\/Akt\/NF-\u03baB signalling is responsible for the protective effect of TNIP3 overexpression on ISO-induced HF. And PI3K\/Akt signalling activation offset the protective effect of TNIP3 overexpression on ISO-induced cardiac inflammation and VAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings of this study highlight the critical role of TNIP3 in ISO-associated cardiac remodelling and VAs, which are induced by the inhibited activation of the PI3K\/Akt\/NF-\u03baB signalling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/europace\/euaf002","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T07:14:53Z","timestamp":1736493293000},"source":"Crossref","is-referenced-by-count":7,"title":["Tumour necrosis factor alpha-induced protein 3-interacting protein 3 overexpression protects against arrhythmogenic remodelling in the heart failure mice"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0024-9204","authenticated-orcid":false,"given":"Hongjie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University , No. 238 Jiefang Road, Wuhan 430060, Hubei ,","place":["P.R. of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Renmin Hospital of Wuhan University , No. 238 Jiefang Road, Wuhan 430060, Hubei ,","place":["P.R. of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital; Institute of Cardiovascular Diseases, China Three Gorges University, Hu Bei Clinical Research Center for Ischemic Cardiovascular Disease , No. 183 Yiling Avenue, Yichang 443000, Hubei ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-7369","authenticated-orcid":false,"given":"Wei","family":"Shuai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Renmin Hospital of Wuhan University , No. 238 Jiefang Road, Wuhan 430060, Hubei ,","place":["P.R. of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"2025013112544023500_euaf002-B1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrcardio.2016.25","article-title":"Epidemiology and aetiology of heart failure","volume":"13","author":"Ziaeian","year":"2016","journal-title":"Nat Rev Cardiol"},{"key":"2025013112544023500_euaf002-B2","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1016\/j.jacc.2019.03.478","article-title":"ACC\/AHA 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