{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:46:08Z","timestamp":1790959568830,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071561"],"award-info":[{"award-number":["82071561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371583"],"award-info":[{"award-number":["82371583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>Doxorubicin (Dox), an anthracycline antibiotic, is widely used in cancer treatment. Although its antitumor efficacy appears significant, its clinical use is greatly restricted by its induction of cardiotoxicity. Cardiac senescence drives the Dox\u2010induced cardiotoxicity, but whether diminishing these\u00a0senescent cardiomyocytes could alleviate the cardiotoxicity remains unclear. Here, we assessed whether senescent cardiomyocytes have a senescence\u2010associated secretory phenotype (SASP) that affects healthy non\u2010senescent cardiomyocytes, rendering them senescent via the delivery of exosomes. Additionally, we explored whether targeting SASP senescent cardiomyocytes using a Bcl\u20102 inhibitor could alleviate cardiotoxicity. Cardiac damage was induced in a mouse model of continuous Dox treatment <jats:italic>in vivo<\/jats:italic>, and cardiomyocytes <jats:italic>in vitro<\/jats:italic>. Immunofluorescence of the senescence markers of Cdkn2a, Cdkn1a and \u03b3\u2010H<jats:sub>2<\/jats:sub>A.X was used to assess the SASP in the Dox\u2010treated heart. To explore the molecular mechanisms involved, the Bcl\u20102 inhibitor ABT\u2010199 was employed to eliminate SASP senescent cardiomyocytes. We show that the cardiomyocytes acquire a SASP during Dox treatment. The senescent cardiomyocytes upregulated Bcl\u20102, although treatment of mice with ABT\u2010199 selectively eliminated SASP senescent cardiomyocytes involved in Dox\u2010induced cardiotoxicity, thus leading to partial alleviation of Dox\u2010induced cardiotoxicity. Moreover, we concluded that SASP factors secreted by senescent cardiomyocytes induced by Dox renders otherwise healthy cardiomyocytes senescent through exosome delivery. Our findings suggest that SASP senescent cardiomyocytes are a significant component of the pathogenesis of Dox\u2010dependent cardiotoxicity and indicate that targeting the clearance of SASP senescent cardiomyocytes could be a new therapeutic approach for Dox\u2010induced cardiac injury.<\/jats:p>","DOI":"10.1111\/febs.17164","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T17:11:01Z","timestamp":1718039461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Depletion of <scp>SASP<\/scp> senescent cardiomyocytes with senolytic drugs confers therapeutic effects in doxorubicin\u2010related cardiotoxicity"],"prefix":"10.1111","author":[{"given":"Wenzheng","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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