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Poly(ADP\u2010ribose) polymerase 1 (PARP1) transfers ADP\u2010ribose groups from donor NAD\n                      <jats:sup>+<\/jats:sup>\n                      molecules onto target substrates upon oxidative stress, which may promote apoptosis and myocardial injury. The detailed molecular pathways of PARP1 activation, however, remain unclear. Here, we found that reactive oxygen species (ROS) function as signalling molecules to promote CBP\u2010mediated PARP1 lactylation in an ATM\u2010dependent manner, which induces PARP1 PARylation and ultimate cell apoptosis. We identified CBP and SIRT1 as specific lactyltransferase and delactylase of PARP1, respectively. Besides, the lactylation of PARP1 depends on the LDHA activity and lactate production. Moreover, Myocardium\u2010specific CBP knockout mice decrease PARP1 lactylation and prevent doxorubicin\u2010induced cardiac dysfunction. Our findings unravelled that excessive oxidative stress\u2010induced ROS accumulation activates the ATM\u2010CBP\u2010PARP1 signalling pathway via a lactylation\u2013PARylation cascade to promote apoptosis and myocardial injury.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70745","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:29:54Z","timestamp":1786951794000},"source":"Crossref","is-referenced-by-count":0,"title":["ROS\u2010ATM\u2010CBP axis\u2010mediated PARP1 lactylation aggravates doxorubicin\u2010induced cardiotoxicity"],"prefix":"10.1002","volume":"16","author":[{"given":"Wenbin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology First Hospital of China Medical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology First Hospital of 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