{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:49:11Z","timestamp":1791496151451,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zebrafish is among the most widely used vertebrate models for defining how environmental toxicants disrupt cardiovascular development, and the adverse outcome pathway (AOP) framework is the standard tool for organizing this mechanistic knowledge for regulatory use. Existing cardiovascular AOPs link molecular initiating events, such as aryl hydrocarbon receptor activation, to apical outcomes including pericardial edema and early life stage mortality through key events (KEs) measured largely at the gene and protein level. MicroRNAs (miRNAs) are recurrently dysregulated intermediates in this same causal chain across many toxicant classes, yet remain absent as formally recognized KEs in the current cardiovascular AOP network. This review synthesizes the zebrafish literature on toxicant-induced cardiovascular malformation, the cardiogenic miRNA circuitry governing chamber formation, looping, valve formation, and electrophysiology, and 14 cardiotoxicity-relevant AOPs catalogued in AOP-Wiki, including both structural and functional cardiac endpoints. Building on this synthesis, we propose a miRNA-bridged KE (miR-BKE) framework that formalizes 6 criteria, 4 adapted from established weight-of-evidence practice, a fifth grounded in miRNA target-validation standards, and a sixth addressing taxonomic and species variability, for admitting specific miRNAs as quantifiable bridging nodes. We apply this framework, with an explicit numerical scoring rubric, across 14 toxicant classes spanning industrial, agricultural, pharmaceutical, and consumer-product chemicals, and identify where genomics and small RNA sequencing data are sufficient, partial, predicted only, or entirely absent for formal KE inclusion. A prioritized research agenda ranks these classes by readiness for miR-BKE admission. The review concludes by discussing the framework\u2019s taxonomic, chemical-mixture, and methodological limitations, and the priority experiments needed to test it.<\/jats:p>","DOI":"10.1093\/etojnl\/vgag254","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:12:04Z","timestamp":1790179924000},"source":"Crossref","is-referenced-by-count":0,"title":["MicroRNAs as bridging key events in zebrafish cardiovascular adverse outcome pathways: A\u00a0cross-chemical evidence synthesis and the microRNA bridged key event framework"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-8301","authenticated-orcid":false,"given":"Rajesh","family":"Pamanji","sequence":"first","affiliation":[{"name":"Department of Microbiology, Pondicherry University , Puducherry,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Koigoora","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Vignan\u2019s Foundation for Science, Technology & Research (Deemed to be University) , Hyderabad,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisha","family":"Sivan","sequence":"additional","affiliation":[{"name":"Division of Medical Research, SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology , Kattankulathur, Chennai,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026100816511601500_vgag254-B1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3390\/cells14070531","article-title":"Zebrafish as a versatile model for cardiovascular research: Peering into the heart of the 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