{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:40Z","timestamp":1792042300490,"version":"4.4.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82270525"],"award-info":[{"award-number":["82270525"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82202272"],"award-info":[{"award-number":["82202272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82470521"],"award-info":[{"award-number":["82470521"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Research and Development Program of Heilongjiang Province","award":["GA23C006"],"award-info":[{"award-number":["GA23C006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,15]]},"abstract":"<jats:p>Lactylation, a posttranslational modification derived from glycolysis, plays a pivotal role in ischemic heart disease. Neutrophils are predominantly glycolytic cells that trigger intensive inflammation of myocardial ischemia\/reperfusion (MI\/R). However, whether lactylation regulates neutrophil function during MI\/R remains unknown. We applied lactyl proteomics analysis and found that S100a9 was lactylated at lysine 26 (S100a9K26la) in neutrophils, with elevated levels observed in both patients with acute myocardial infarction (AMI) and MI\/R model mice. We demonstrated that S100a9K26la drove the development of MI\/R using mutant knockin mice. Mechanistically, lactylated S100a9 translocated to the nucleus of neutrophils, where it bound to the promoters of migration-related genes, thereby enhancing their transcription as a coactivator and promoting neutrophil migration and cardiac recruitment. Additionally, lactylated S100a9 was released during neutrophil extracellular trap (NET) formation, leading to cardiomyocyte death by disrupting mitochondrial function. The enzyme dihydrolipoyllysine-residue acetyltransferase (DLAT) was identified as the lactyltransferase facilitating neutrophil S100a9K26la following MI\/R, a process that could be restrained by \u03b1-lipoic acid. Consistently, we found that targeting the DLAT\/S100a9K26la axis suppressed neutrophil burden and improved cardiac function following MI\/R. In patients with AMI, elevated S100a9K26la levels in plasma were positively correlated with cardiac death. These findings highlight S100a9 lactylation as a potential therapeutic target for MI\/R and as a promising biomarker for evaluating poor MI\/R outcomes.<\/jats:p>","DOI":"10.1172\/jci194664","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:00:23Z","timestamp":1760025623000},"source":"Crossref","is-referenced-by-count":28,"title":["S100a9 lactylation triggers neutrophil trafficking and cardiac inflammation in myocardial ischemia\/reperfusion injury"],"prefix":"10.1172","volume":"135","author":[{"given":"Xiaoqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China."},{"name":"The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, 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