{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:20Z","timestamp":1785421700668,"version":"3.56.0"},"reference-count":158,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of Poland"},{"id":[{"id":"https:\/\/ror.org\/05dwvd537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The mechanisms underlying doxorubicin (DOX) cardiotoxicity include activation of the renin\u2013angiotensin\u2013aldosterone system (RAAS), oxidative stress, mitochondrial dysfunction, calcium overload, and cardiomyocyte apoptosis. Cortisol plays a key role in regulating multiple metabolic, immunological, cardiovascular, and neuroendocrine processes and may additionally influence drug pharmacokinetics by modulating the activity of P-glycoprotein (P-gp). The peptide apelin, through its specific target, angiotensin II protein J receptor (APJ), exerts cardioprotective, antifibrotic, and anti-inflammatory effects. The available data demonstrate that apelin signaling protects against DOX-induced cardiotoxicity, impacts cortisol secretion, and inhibits RAAS. Short-term elevation in cortisol levels, caused by apelin, may reduce inflammation and thus have cardioprotective properties. However, through chronically elevated cortisol levels, apelin may indirectly contribute to peripheral resistance, cardiac remodeling, and myocardial damage, especially when cortisol metabolism by 11\u03b2-hydroxysteroid dehydrogenase 2 (11\u03b2-HSD2) is altered. This narrative review explores the potential molecular and cellular mechanisms shaping the outcome of apelin\u2013cortisol interplay, offering a potential foundation for developing cardioprotective strategies during anticancer therapy. Future studies should be aimed at assessing the complex interactions between cortisol, apelin, and the RAAS regarding DOX-induced cardiotoxicity.<\/jats:p>","DOI":"10.3390\/cells15131187","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apelin, Cortisol, and Doxorubicin-Induced Cardiotoxicity: A Triangle of Actions"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8109-0610","authenticated-orcid":false,"given":"Kinga","family":"Dziobiak","sequence":"first","affiliation":[{"name":"Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1116-7327","authenticated-orcid":false,"given":"Maja","family":"Owe-Larsson","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Centre of Biostructure Research, Medical University of Warsaw, Cha\u0142ubi\u0144skiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miros\u0142awa","family":"Chwil","sequence":"additional","affiliation":[{"name":"Department of Botany and Plant Physiology, University of Life Sciences in Lublin, Akademicka 15, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-8401","authenticated-orcid":false,"given":"Izabela R\u00f3\u017ca","family":"Janiuk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Centre of Biostructure Research, Medical University of Warsaw, Cha\u0142ubi\u0144skiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.2174\/092986709788803312","article-title":"Doxorubicin: The good, the bad and the ugly effect","volume":"16","author":"Carvalho","year":"2009","journal-title":"Curr. 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