{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T10:45:02Z","timestamp":1782729902013,"version":"3.54.5"},"reference-count":75,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNF\u03b1 (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">Lactobacillus casei<\/jats:italic>\n              cell wall extract\u2013induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNF\u03b1 neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1\u03b2 and TNF\u03b1, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNF\u03b1 neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNF\u03b1 neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of\n              <jats:italic toggle=\"yes\">L casei<\/jats:italic>\n              cell wall extract\u2013injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway,\n              <jats:italic toggle=\"yes\">L casei<\/jats:italic>\n              cell wall extract induced spontaneous ventricular tachycardia and premature deaths.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              Our results characterize the electrophysiological abnormalities associated with\n              <jats:italic toggle=\"yes\">L casei<\/jats:italic>\n              cell wall extract\u2013induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNF\u03b1 therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320382","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T10:03:59Z","timestamp":1708596239000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-5745","authenticated-orcid":true,"given":"Thassio","family":"Mesquita","sequence":"first","affiliation":[{"name":"Smidt Heart Institute (T.M., Y.-N.L., R.M.-d.-S., M.A., E.C.), Cedars-Sinai Medical Center, Los Angeles, 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