{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:49:54Z","timestamp":1776898194069,"version":"3.51.2"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":293,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislaufforschung","doi-asserted-by":"publisher","award":["81Z0100212"],"award-info":[{"award-number":["81Z0100212"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislaufforschung","doi-asserted-by":"publisher","award":["81Z0100212"],"award-info":[{"award-number":["81Z0100212"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Anthracyclines are key components of various chemotherapy regimens, but their clinical utility is limited by severe cardiotoxic side effects. Previous studies have suggested that anthracycline-induced cardiotoxicity (AIC) may be driven by alterations in myocardial lipid metabolism. This study aimed to systematically explore the cardiac lipidomic landscape of AIC with regard to potential pathomechanisms and novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Mass spectrometry-based untargeted lipidomics were performed on myocardial biopsies from 13 patients with AIC (age 53\u2009\u00b1\u200931\u2009years, 54% female, left ventricular ejection fraction 19\u2009\u00b1\u20094%) and 15 age- and sex-matched controls. Lipidomic profiles were also compared with 15 patients with other heart failure aetiologies (matched for sex and age). A total of 627 individual lipid species from 22 different lipid classes were analysed. AIC was associated with a lower proportion of polyunsaturated fatty acids towards more monounsaturated and saturated sidechains as well as significant alterations in the proportion of odd-chain fatty acids. Pathway analyses indicated a higher precursor conversion into lysolipids in AIC. This accumulation of lysolipid species was not observed in other heart failure aetiologies and may represent a specific finding in AIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Anthracycline-induced cardiotoxicity leads to distinct alterations of the myocardial lipidome. Increased levels of myocardial lysolipids were identified as a novel lipidomic trait in AIC, which appears to be distinct from other causes of heart failure. Further research studying pharmacological interventions in lysolipid metabolism for prevention and therapy of AIC is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3656","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T21:09:38Z","timestamp":1746133778000},"page":"1056-1066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cancer Therapy-related Cardiotoxicity is Associated with Distinct Alterations of the Myocardial Lipidome"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1730-8931","authenticated-orcid":false,"given":"Vera M.","family":"Braun","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Foryst-Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0214-3203","authenticated-orcid":false,"given":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9 , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-0797","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Baczk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged , Szeged ,","place":["Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-0007","authenticated-orcid":false,"given":"Hendrik","family":"Milting","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW , Bad Oeynhausen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-0990","authenticated-orcid":false,"given":"Ulrich","family":"Kintscher","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-2336","authenticated-orcid":false,"given":"Niklas","family":"Beyhoff","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9 , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"key":"2026021721481827100_ejhf3656-bib-0001","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrcardio.2015.65","article-title":"Cardiotoxicity of anticancer treatments","volume":"12","author":"Ewer","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"2026021721481827100_ejhf3656-bib-0002","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41569-020-0348-1","article-title":"Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia","volume":"17","author":"Herrmann","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"2026021721481827100_ejhf3656-bib-0003","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.jacc.2014.06.1167","article-title":"Prevention of anthracycline-induced cardiotoxicity: Challenges and opportunities","volume":"64","author":"Vejpongsa","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026021721481827100_ejhf3656-bib-0004","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/eurheartj\/ehaa006","article-title":"Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: The CARDIOTOX registry","volume":"41","author":"L\u00f3pez-Send\u00f3n","year":"2020","journal-title":"Eur Heart J"},{"key":"2026021721481827100_ejhf3656-bib-0005","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/nm.2919","article-title":"Identification of the molecular basis of doxorubicin-induced cardiotoxicity","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat Med"},{"key":"2026021721481827100_ejhf3656-bib-0006","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J Clin Investig"},{"key":"2026021721481827100_ejhf3656-bib-0007","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1016\/0006-2952(80)90050-7","article-title":"Evidence of a complex between adriamycin derivatives and cardiolipin: Possible role in cardiotoxicity","volume":"29","author":"Goormaghtigh","year":"1980","journal-title":"Biochem Pharmacol"},{"key":"2026021721481827100_ejhf3656-bib-0008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0005-2736(80)90145-5","article-title":"Evidence of a specific complex between adriamycin and negatively-charged phospholipids","volume":"597","author":"Goormaghtigh","year":"1980","journal-title":"Biochim Biophys Acta"},{"key":"2026021721481827100_ejhf3656-bib-0009","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0925-4439(90)90014-G","article-title":"Comparable interaction of doxorubicin with various acidic phospholipids results in changes of lipid order and dynamics","volume":"1096","author":"Wolf","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"2026021721481827100_ejhf3656-bib-0010","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/s41598-018-37862-3","article-title":"Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration","volume":"9","author":"Abdullah","year":"2019","journal-title":"Sci Rep"},{"key":"2026021721481827100_ejhf3656-bib-0011","doi-asserted-by":"crossref","first-page":"22155","DOI":"10.1038\/s41598-023-48184-4","article-title":"Molecular assessment of drug-phospholipid interactions consequent to cancer treatment: A study of anthracycline-induced cardiotoxicity","volume":"13","author":"Ahmed","year":"2023","journal-title":"Sci Rep"},{"key":"2026021721481827100_ejhf3656-bib-0012","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.jchf.2022.03.006","article-title":"Sodium-glucose co-transporter-2 inhibitors and cardiac outcomes among patients treated with anthracyclines","volume":"10","author":"Gongora","year":"2022","journal-title":"JACC Heart Fail"},{"key":"2026021721481827100_ejhf3656-bib-0013","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1001\/jama.2023.11887","article-title":"Atorvastatin for anthracycline-associated cardiac dysfunction: The STOP-CA randomized clinical trial","volume":"330","author":"Neilan","year":"2023","journal-title":"JAMA"},{"key":"2026021721481827100_ejhf3656-bib-0014","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejim.2024.04.007","article-title":"Cardio-protective effects of statins in patients undergoing anthracycline-based chemotherapy: An updated meta-analysis of randomized controlled trials","volume":"126","author":"Felix","year":"2024","journal-title":"Eur J Intern Med"},{"key":"2026021721481827100_ejhf3656-bib-0015","doi-asserted-by":"crossref","first-page":"19364","DOI":"10.1038\/s41598-021-98702-5","article-title":"Mouse lipidomics reveals inherent flexibility of a mammalian lipidome","volume":"11","author":"Surma","year":"2021","journal-title":"Sci Rep"},{"key":"2026021721481827100_ejhf3656-bib-0016","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1073\/pnas.0811700106","article-title":"Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry","volume":"106","author":"Ejsing","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021721481827100_ejhf3656-bib-0017","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/ejlt.201500145","article-title":"An automated shotgun lipidomics platform for high throughput, comprehensive, and quantitative analysis of blood plasma intact lipids","volume":"117","author":"Surma","year":"2015","journal-title":"Eur J Lipid Sci Technol"},{"key":"2026021721481827100_ejhf3656-bib-0018","doi-asserted-by":"crossref","first-page":"R8","DOI":"10.1186\/gb-2011-12-1-r8","article-title":"A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language","volume":"12","author":"Herzog","year":"2011","journal-title":"Genome Biol"},{"key":"2026021721481827100_ejhf3656-bib-0019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029851","article-title":"LipidXplorer: A software for consensual cross-platform lipidomics","volume":"7","author":"Herzog","year":"2012","journal-title":"PLoS One"},{"key":"2026021721481827100_ejhf3656-bib-0020","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","article-title":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","volume":"43","author":"Lyon","year":"2022","journal-title":"Eur Heart J"},{"key":"2026021721481827100_ejhf3656-bib-0021","doi-asserted-by":"crossref","first-page":"4","DOI":"10.12688\/f1000research.28022.1","article-title":"BioPAN: A web-based tool to explore mammalian lipidome metabolic pathways on LIPID MAPS","volume":"10","author":"Gaud","year":"2021","journal-title":"F1000Res"},{"key":"2026021721481827100_ejhf3656-bib-0022","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/clpt.2014.174","article-title":"Serendipity and the discovery of novel compounds that restore mitochondrial plasticity","volume":"96","author":"Szeto","year":"2014","journal-title":"Clin Pharmacol Ther"},{"key":"2026021721481827100_ejhf3656-bib-0023","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3892\/ijmm.2021.4896","article-title":"Peptide Szeto-Schiller 31 ameliorates doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway","volume":"47","author":"Zhang","year":"2021","journal-title":"Int J Mol Med"},{"key":"2026021721481827100_ejhf3656-bib-0024","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0014-5793(91)81043-8","article-title":"Characterization of the interaction of doxorubicin with (poly)phosphoinositides in model systems evidence for specific interaction with phosphatidylinositol-monophosphate and -diphosphate","volume":"288","author":"Wolf","year":"1991","journal-title":"FEBS Lett"},{"key":"2026021721481827100_ejhf3656-bib-0025","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s12967-024-05088-9","article-title":"Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: A study in HER2-positive and HER2-negative breast cancer patients","volume":"22","author":"Thonusin","year":"2024","journal-title":"J Transl Med"},{"key":"2026021721481827100_ejhf3656-bib-0026","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20210579","article-title":"New appreciation for an old pathway: The lands cycle moves into new arenas in health and disease","volume":"50","author":"O'Donnell","year":"2022","journal-title":"Biochem Soc Trans"},{"key":"2026021721481827100_ejhf3656-bib-0027","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1194\/jlr.R046391","article-title":"Autotaxin: Structure-function and signaling","volume":"55","author":"Perrakis","year":"2014","journal-title":"J Lipid Res"},{"key":"2026021721481827100_ejhf3656-bib-0028","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242115693","article-title":"Review of eukaryote cellular membrane lipid composition, with special attention to the fatty acids","volume":"24","author":"Ali","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026021721481827100_ejhf3656-bib-0029","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.freeradbiomed.2022.06.228","article-title":"Half is enough: Oxidized lysophospholipids as novel bioactive molecules","volume":"188","author":"Petan","year":"2022","journal-title":"Free Radical Biol Med"},{"key":"2026021721481827100_ejhf3656-bib-0030","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s10741-020-10063-9","article-title":"Oxidative stress and inflammation: Determinants of anthracycline cardiotoxicity and possible therapeutic targets","volume":"26","author":"Fabiani","year":"2021","journal-title":"Heart Fail Rev"},{"key":"2026021721481827100_ejhf3656-bib-0031","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41392-020-00367-5","article-title":"Role of lysophosphatidic acid and its receptors in health and disease: Novel therapeutic strategies","volume":"6","author":"Geraldo","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2026021721481827100_ejhf3656-bib-0032","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2018.01315","article-title":"Lysophosphatidic acid is associated with cardiac dysfunction and hypertrophy by suppressing autophagy via the LPA3\/AKT\/mTOR pathway","volume":"9","author":"Yang","year":"2018","journal-title":"Front Physiol"},{"key":"2026021721481827100_ejhf3656-bib-0033","article-title":"Ablation of lysophosphatidic acid receptor 1 attenuates hypertrophic cardiomyopathy in a mouse model","volume":"119","author":"Axelsson Raja","year":"2022","journal-title":"Proc Natl Acad Sci U\u2009S\u2009A"},{"key":"2026021721481827100_ejhf3656-bib-0034","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41598-018-36914-y","article-title":"The impact of cardiac lipotoxicity on cardiac function and miRNAs signature in obese and non-obese rats with myocardial infarction","volume":"9","author":"Mar\u00edn-Royo","year":"2019","journal-title":"Sci Rep"},{"key":"2026021721481827100_ejhf3656-bib-0035","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1042\/bj3620023","article-title":"Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2) attenuates mitochondrial phospholipid loss and is cardioprotective","volume":"362","author":"Williams","year":"2002","journal-title":"Biochem J"},{"key":"2026021721481827100_ejhf3656-bib-0036","first-page":"5992","article-title":"Inhibition of membrane-associated calcium-independent phospholipase A2 as a potential culprit of anthracycline cardiotoxicity","volume":"63","author":"Swift","year":"2003","journal-title":"Cancer Res"},{"key":"2026021721481827100_ejhf3656-bib-0037","doi-asserted-by":"crossref","first-page":"5470","DOI":"10.1021\/acs.chemrev.3c00701","article-title":"Lysophosphatidylserine: A signaling lipid with implications in human diseases","volume":"124","author":"Chakraborty","year":"2024","journal-title":"Chem Rev"},{"key":"2026021721481827100_ejhf3656-bib-0038","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1038\/s41467-023-40201-4","article-title":"Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34","volume":"14","author":"Sugihara","year":"2023","journal-title":"Nat Commun"},{"key":"2026021721481827100_ejhf3656-bib-0039","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.chest.2018.08.1058","article-title":"Randomized, double-blind, placebo-controlled, phase 2 trial of BMS-986020, a lysophosphatidic acid receptor antagonist for the treatment of idiopathic pulmonary fibrosis","volume":"154","author":"Palmer","year":"2018","journal-title":"Chest"},{"key":"2026021721481827100_ejhf3656-bib-0040","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1002\/art.40547","article-title":"Lysophosphatidic acid receptor 1 antagonist SAR100842 for patients with diffuse cutaneous systemic sclerosis: A double-blind, randomized, eight-week placebo-controlled study followed by a sixteen-week open-label extension study","volume":"70","author":"Allanore","year":"2018","journal-title":"Arthritis Rheumatol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/27\/6\/1056\/66824911\/eurjhf_27_6_1056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/27\/6\/1056\/66824911\/eurjhf_27_6_1056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T02:48:34Z","timestamp":1771382914000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/27\/6\/1056\/8468445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,1]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,5,1]]},"published-print":{"date-parts":[[2025,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.3656","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,5,1]]},"assertion":[{"value":"2024-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}