{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:09:15Z","timestamp":1778875755365,"version":"3.51.4"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program of Shandong Province","award":["2022ZLGX03"],"award-info":[{"award-number":["2022ZLGX03"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82302466,82325031,82030059"],"award-info":[{"award-number":["82302466,82325031,82030059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Natural Science Regional Innovation Fund","award":["U23A20485"],"award-info":[{"award-number":["U23A20485"]}]},{"name":"Taishan Pandeng Scholar Program of Shandong Province","award":["tspd20240819"],"award-info":[{"award-number":["tspd20240819"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZR2023QH220"],"award-info":[{"award-number":["ZR2023QH220"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Distinguished Physician Program, Taishan Pandeng Scholar Program of Shandong Province","award":["tspd20240819"],"award-info":[{"award-number":["tspd20240819"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:p>\n                    Heart failure (HF) persists as the primary cause of death among patients recovering from acute myocardial infarction (AMI). Protein ubiquitination has been implicated as a key modulator of HF pathogenesis, yet the role of ubiquitination in the\n                    <jats:italic>Aldh2<\/jats:italic>\n                    rs671 mutant \u2014 the most common single-nucleotide variant in human populations \u2014 remains poorly understood. We discovered TRIM21 as a previously unrecognized E3 ubiquitin ligase for the ALDH2 rs671 mutant and elucidated its mechanistic involvement in HF progression. Using\n                    <jats:italic>Aldh2<\/jats:italic>\n                    BM chimeric mice to model AMI, we observed that WT mice transplanted with\n                    <jats:italic>Aldh2<\/jats:italic>\n                    rs671 donor BM developed severe myocardial fibrosis and markedly reduced cardiac systolic function 2 weeks after infarction compared with controls. This phenotype arose from defective macrophage efferocytosis caused by myeloid-specific\n                    <jats:italic>Aldh2<\/jats:italic>\n                    rs671 mutation. Through high-resolution mass spectrometry proteomics, we identified TRIM21 as the E3 ligase targeting ALDH2. TRIM21 catalyzed K48-linked ubiquitination at ALDH2 lysine 73. Macrophage-specific\n                    <jats:italic>Trim21<\/jats:italic>\n                    knockdown via AAV-sh\n                    <jats:italic>Trim21<\/jats:italic>\n                    reversed both the exacerbated cardiac fibrosis and systolic dysfunction by restoring macrophage efferocytosis. These findings delineate the upstream E3 ubiquitin ligase and the ubiquitination site of ALDH2, revealing a potential therapeutic target for HF.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.197555","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:01:08Z","timestamp":1771952468000},"source":"Crossref","is-referenced-by-count":0,"title":["E3 ubiquitin ligase TRIM21-mediated K48-linked ubiquitination of ALDH2 rs671 mutant promotes adverse cardiac remodeling"],"prefix":"10.1172","volume":"11","author":[{"given":"Tianrui","family":"Han","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, 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Drug, Qilu Hospital of Shandong University, Jinan, China."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China\u2019s Ministry of Education, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China."},{"name":"NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China."},{"name":"National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangkai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Shandong 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