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This study aimed to explore the role of melatonin in Kawasaki disease (KD)\u2010associated vasculitis and its underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>The role of melatonin was evaluated in human coronary artery endothelial cells (HCAECs), peripheral blood mononuclear cells from KD patients, human THP1 cell line in vitro, and a <jats:italic>Candida albicans<\/jats:italic> water\u2010soluble fraction (CAWS)\u2010induced KD mouse model in vivo. Cell proliferation assay, cell apoptosis assay, cell co\u2010culture, RNA extraction, RNA sequencing, reverse transcription quantitative PCR, enzyme\u2010linked immunosorbent assay (ELISA), transwell assay, western blot, dual\u2010luciferase reporter assay, and autophagic flux assay were performed to investigate the function and regulatory mechanisms of melatonin in vitro, while haematoxylin and eosin staining, Verhoeff's van Gieson staining, ELISA, and immunohistochemical analysis were performed to detect the effect of melatonin in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Melatonin suppressed cell apoptosis directly reduced the expression of endothelial cell damage markers in HCAECs, and alleviated vasculitis in the CAWS\u2010induced KD mouse model. Mechanistically, melatonin promoted autophagy by activating the melatonin\/ melatonin receptor (MT)\/cAMP\u2010response element binding protein (CREB) pathway and upregulating the expression of autophagy\u2010related gene\u20103, thereby suppressing cell apoptosis in an autophagy\u2010dependent manner. Additionally, melatonin decreased the production of pro\u2010inflammatory cytokines in macrophages and indirectly reduced the immunopathological damage of HCAECs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study revealed that melatonin protects vascular endothelial cells in KD, by suppressing cell apoptosis in an autophagy\u2010dependent manner and reducing the immunopathological damage mediated by macrophages.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13251","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T06:32:54Z","timestamp":1652855574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Melatonin alleviates vascular endothelial cell damage by regulating an autophagy\u2010apoptosis axis in Kawasaki disease"],"prefix":"10.1111","volume":"55","author":[{"given":"Yuanzheng","family":"Zheng","sequence":"first","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saihua","family":"Huang","sequence":"additional","affiliation":[{"name":"National Health Commission (NHC) Key Laboratory of Neonatal Diseases Fudan University  Shanghai China"},{"name":"Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"},{"name":"National Health Commission (NHC) Key Laboratory of Neonatal 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