{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T11:04:51Z","timestamp":1781003091535,"version":"3.54.1"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":159,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["RS-2024-00346434"],"award-info":[{"award-number":["RS-2024-00346434"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2020R1I1A1A01067800"],"award-info":[{"award-number":["2020R1I1A1A01067800"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    mRNA vaccine\u2010associated myocarditis is a rare but clinically important adverse event whose pathogenesis remains incompletely understood. Initial hypotheses focused primarily on the spike protein antigen, with growing preclinical evidence implicating the lipid nanoparticle (LNP) delivery system as an additional and potentially important contributor to myocardial inflammation. Here, we propose a multi\u2010hit model that integrates LNP\u2010driven mechanisms as a central pathogenic axis, initiated by the systemic distribution and accumulation of LNPs in the heart. While the mRNA payload is cleared within days, the synthetic ionizable lipids \u2010ALC\u20100315 (BNT162b2) and SM\u2010102 (mRNA\u20101273) persist significantly longer than the mRNA payload itself. These two lipids differ in biodegradability and pharmacokinetic distinctions, together with differences in lipid dose and formulation, they may contribute to the divergent myocarditis rates observed between the two vaccine products. In this suggesting review, the first hit\u201d involves the disruption of myocardial energy metabolism by these lipids, which can integrate into cellular membranes and impair mitochondrial fatty acid oxidation. This is compounded by a second hit of direct innate immune activation, preclinical studies demonstrate that LNPs engage pattern\u2010recognition receptors (PRRs) like toll\u2010like receptors (TLRs) and the NLRP3 inflammasome, leading to the release of pro\u2010inflammatory cytokines such as IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    and IL\u201018. Inflammation is then amplified via Damage\u2010associated molecular patterns (DAMPs) released from stressed cardiomyocytes. The clinical outcome\u2014ranging from self\u2010limited mild myocarditis to fulminant disease with diverse histopathological patterns\u2014is likely shaped by host susceptibility factors, including sex hormones, genetic predisposition, and prior immune priming, that modulate the intensity of this pathogenic cascade.\n                  <\/jats:p>","DOI":"10.1155\/mi\/8991922","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T10:54:32Z","timestamp":1781002472000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myocarditis After mRNA Vaccination: A Metabolic\u2013Innate Immune Cascade Centered on Lipid 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