{"title":"乙酰辅酶a短链合成酶-2通过靶向组蛋白乙酰化调控心肌缺血/再灌注损伤","authors":"Xinhui Chen, Qingling Xu, Wei Ding, Yu Wang, Puhan Wang, Chunyige Zhao, Xiang Ao, Jianxun Wang","doi":"10.1007/s12265-025-10657-4","DOIUrl":null,"url":null,"abstract":"<p><p>Myocardial infarction (MI) remains a leading cause of mortality, and although reperfusion therapy is essential for myocardial salvage, it often results in ischemia-reperfusion (I/R) injury, which contributes substantially to cardiomyocyte necrosis. Although the mechanisms of cardiomyocyte necrosis remain unclear, we identified ACSS2 as a key regulator in myocardial I/R injury. ACSS2 was upregulated under oxidative stress and I/R conditions. Its knockdown reduced necrosis, while overexpression aggravated it. Mechanistically, nuclear translocation of ACSS2 enhanced H3K9 acetylation and activated necrosis-related genes. In vivo, ACSS2 silencing alleviated myocardial injury and improved cardiac function. These findings reveal that ACSS2 promotes necrosis via nuclear acetyl-CoA production and epigenetic regulation, offering a potential therapeutic target for I/R injury.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Acetyl-CoA Short-Chain Synthetase-2 Regulates Myocardial Ischemia/Reperfusion Injury by Targeting Histone Acetylation.\",\"authors\":\"Xinhui Chen, Qingling Xu, Wei Ding, Yu Wang, Puhan Wang, Chunyige Zhao, Xiang Ao, Jianxun Wang\",\"doi\":\"10.1007/s12265-025-10657-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myocardial infarction (MI) remains a leading cause of mortality, and although reperfusion therapy is essential for myocardial salvage, it often results in ischemia-reperfusion (I/R) injury, which contributes substantially to cardiomyocyte necrosis. Although the mechanisms of cardiomyocyte necrosis remain unclear, we identified ACSS2 as a key regulator in myocardial I/R injury. ACSS2 was upregulated under oxidative stress and I/R conditions. Its knockdown reduced necrosis, while overexpression aggravated it. Mechanistically, nuclear translocation of ACSS2 enhanced H3K9 acetylation and activated necrosis-related genes. In vivo, ACSS2 silencing alleviated myocardial injury and improved cardiac function. These findings reveal that ACSS2 promotes necrosis via nuclear acetyl-CoA production and epigenetic regulation, offering a potential therapeutic target for I/R injury.</p>\",\"PeriodicalId\":15224,\"journal\":{\"name\":\"Journal of Cardiovascular Translational Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cardiovascular Translational Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12265-025-10657-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiovascular Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12265-025-10657-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Myocardial infarction (MI) remains a leading cause of mortality, and although reperfusion therapy is essential for myocardial salvage, it often results in ischemia-reperfusion (I/R) injury, which contributes substantially to cardiomyocyte necrosis. Although the mechanisms of cardiomyocyte necrosis remain unclear, we identified ACSS2 as a key regulator in myocardial I/R injury. ACSS2 was upregulated under oxidative stress and I/R conditions. Its knockdown reduced necrosis, while overexpression aggravated it. Mechanistically, nuclear translocation of ACSS2 enhanced H3K9 acetylation and activated necrosis-related genes. In vivo, ACSS2 silencing alleviated myocardial injury and improved cardiac function. These findings reveal that ACSS2 promotes necrosis via nuclear acetyl-CoA production and epigenetic regulation, offering a potential therapeutic target for I/R injury.
期刊介绍：
Journal of Cardiovascular Translational Research (JCTR) is a premier journal in cardiovascular translational research.
JCTR is the journal of choice for authors seeking the broadest audience for emerging technologies, therapies and diagnostics, pre-clinical research, and first-in-man clinical trials.
JCTR''s intent is to provide a forum for critical evaluation of the novel cardiovascular science, to showcase important and clinically relevant aspects of the new research, as well as to discuss the impediments that may need to be overcome during the translation to patient care.
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