{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:25:53Z","timestamp":1791890753158,"version":"4.3.4"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101088919"],"award-info":[{"award-number":["101088919"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chemical-induced heart toxicity remains a major challenge in drug development and environmental safety, largely because current testing often relies on narrow, late-stage endpoints that miss the complex biological progression of the toxicities. To address this, we developed a comprehensive Adverse Outcome Pathway (AOP) network that maps how early (bio) chemical triggers evolve into organ-level dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>By integrating data from the OECD AOP-Wiki, we constructed a unified network of 64 biological events and 94 documented relationships that identifies the critical biological \u201ccrossroads\u201d where different toxic chemicals converge to cause heart damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\/discussion<\/jats:title>\n                    <jats:p>Our analysis reveals a compact core of central biological events, such as oxidative stress and mitochondrial dysfunction, which act as the primary drivers of cardiac injury. This network approach moves beyond single, linear pathways to show how systemic factors, including interactions with other organs like the kidneys, contribute to cardiotoxicity. To translate these findings into a practical resource for the broader scientific community, we developed a methods catalogue that links these biological events to specific laboratory assays. To ensure this work is accessible and actionable, we hosted the network on an interactive, FAIRaligned web platform. By providing a clear scaffold for understanding heart safety, this resource enables the design of more human-relevant, animal-free testing strategies and helps prioritise the most impactful biomarkers for future safety assessments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftox.2026.1781536","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:15:40Z","timestamp":1779120940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiotoxicity adverse outcome pathway network: towards mechanistic and quantitative modelling"],"prefix":"10.3389","volume":"8","author":[{"given":"Luiz","family":"Ladeira","sequence":"first","affiliation":[{"name":"Biomechanics Research Unit, GIGA Institute, University of Li\u00e8ge","place":["Li\u00e8ge, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon A.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University","place":["Utrecht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinde","family":"Masereeuw","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University","place":["Utrecht, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbet","family":"Geris","sequence":"additional","affiliation":[{"name":"Biomechanics Research Unit, GIGA Institute, University of Li\u00e8ge","place":["Li\u00e8ge, Belgium"]},{"name":"Skeletal Biology and Engineering Research Center, KU Leuven","place":["Leuven, Belgium"]},{"name":"Biomechanics Section, Department of Mechanical Engineering, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Staumont","sequence":"additional","affiliation":[{"name":"Biomechanics Research Unit, GIGA Institute, University of Li\u00e8ge","place":["Li\u00e8ge, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/etc.34","article-title":"Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment","volume":"29","author":"Ankley","year":"2009","journal-title":"Environ. 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