{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:18:30Z","timestamp":1787818710503,"version":"build-2784847793"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Atherosclerosis is a chronic inflammatory disease shaped by interactions among vascular cells, innate immunity, adaptive immunity, and metabolic stress. Interleukin-18 (IL-18), an IL-1 superfamily cytokine activated predominantly downstream of inflammasomes, links vascular injury to type 1 immune responses. This structured narrative review integrates mechanistic, plaque-tissue, epidemiological, genetic, and therapeutic evidence for IL-18 in atherosclerosis. Experimental studies generally support pro-atherogenic actions, but these effects vary by plaque stage, cellular context, and genetic background. Human studies consistently show enrichment of IL-18 in inflamed plaques, whereas circulating IL-18 has limited independent diagnostic or prognostic performance after multivariable adjustment in several large cohorts. Drug-target Mendelian randomization supports associations with selected cardiovascular outcomes, but does not substitute for randomized clinical evidence and remains vulnerable to pleiotropy, instrument strength, ancestry, and lifelong-exposure assumptions. Direct IL-18 inhibitors have entered clinical development in inflammatory diseases, yet cardiovascular outcome efficacy has not been established. We therefore position IL-18 as a biologically plausible but unvalidated cardiovascular target and outline a stage-gated translational agenda centered on free IL-18 assays, plaque-context biomarkers, pharmacology, patient selection, and long-term safety.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1910314","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:42:40Z","timestamp":1787816560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-18 in atherosclerosis: context-dependent biology, human evidence, and translational challenges"],"prefix":"10.3389","volume":"13","author":[{"given":"Dongshuai","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, 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