{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:38:45Z","timestamp":1790131125572,"version":"4.0.1"},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"21","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070330"],"award-info":[{"award-number":["82070330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200348"],"award-info":[{"award-number":["82200348"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: The inflammatory response and subsequent ventricular remodeling are key factors contributing to ventricular arrhythmias (VAs) after myocardial infarction (MI). Ubiquitin-specific protease 38 (USP38) is a member of the USP family, but the impact of USP38 in arrhythmia substrate generation after MI remains unclear. This study aimed to determine the role of USP38 in post-MI VAs and its underlying mechanisms.<\/jats:p>\n               <jats:p>Methods and results: Surgical left descending coronary artery ligation was used to construct MI models. Morphological, biochemical, histological, and electrophysiological studies and molecular analyses were performed after MI on days 3 and 28. We found that the USP38 expression was remarkably increased after MI. Cardiac-conditional USP38 knockout (USP38-CKO) reduces the expression of the inflammatory marker CD68 as well as the inflammatory factors TNF-\u03b1 and IL-1\u03b2 after MI, thereby alleviating advanced cardiac fibrosis, electrical remodeling, ion channel remodeling, and susceptibility to VAs. In contrast, cardiac-specific USP38 overexpression (USP38-TG) showed a significant opposite effect, exacerbating the early inflammatory response and cardiac remodeling after MI. Mechanistically, USP38 knockout inhibited activation of the TAK1\/NF-\u03baB signaling pathway after MI, whereas USP38 overexpression enhanced activation of the TAK1\/NF-\u03baB signaling pathway after MI.<\/jats:p>\n               <jats:p>Conclusions: Our study confirms that USP38-CKO attenuates the inflammatory response, improves ventricular remodeling after myocardial infarction, and reduces susceptibility to malignant VA by inhibiting the activation of the TAK1\/NF-\u03baB pathway, with USP38-TG playing an opposing role. These results suggest that USP38 may be an important target for the treatment of cardiac remodeling and arrhythmias after MI.<\/jats:p>","DOI":"10.1042\/cs20230728","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T19:34:44Z","timestamp":1698694484000},"page":"1665-1681","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["USP38 regulates inflammatory cardiac remodeling after myocardial infarction"],"prefix":"10.1042","volume":"137","author":[{"given":"Yang","family":"Gong","sequence":"first","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Kong","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shuai","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-2733","authenticated-orcid":false,"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"1Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China"},{"name":"2Cardiovascular Research Institute of Wuhan University, Wuhan, China"},{"name":"3Hubei Key Laboratory of Cardiology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"2023111507211865600_B1","doi-asserted-by":"publisher","first-page":"789","DOI":"10.11909\/j.issn.1671-5411.2016.09.006","article-title":"Epidemiology and genetics of ventricular fibrillation during acute myocardial infarction","volume":"13","author":"Glinge","year":"2016","journal-title":"J. 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