Melatonin alleviates vascular endothelial cell damage by regulating an autophagy-apoptosis axis in Kawasaki disease

Objectives Melatonin has been reported to be an appropriate candidate for mitigating various cardiovascular injuries, owing to its versatility. This study aimed to explore the role of melatonin in Kawasaki disease (KD)-associated vasculitis and its underlying mechanisms. Material and Methods 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 Candida albicans water-soluble fraction (CAWS)-induced KD mouse model in vivo. Cell proliferation assay, cell apoptosis assay, cell co-culture, RNA extraction, RNA sequencing, reverse transcription quantitative PCR, enzyme-linked immunosorbent assay (ELISA), transwell assay, western blot, dual-luciferase 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. Results Melatonin suppressed cell apoptosis directly reduced the expression of endothelial cell damage markers in HCAECs, and alleviated vasculitis in the CAWS-induced KD mouse model. Mechanistically, melatonin promoted autophagy by activating the melatonin/ melatonin receptor (MT)/cAMP-response element binding protein (CREB) pathway and upregulating the expression of autophagy-related gene-3, thereby suppressing cell apoptosis in an autophagy-dependent manner. Additionally, melatonin decreased the production of pro-inflammatory cytokines in macrophages and indirectly reduced the immunopathological damage of HCAECs. Conclusions This study revealed that melatonin protects vascular endothelial cells in KD, by suppressing cell apoptosis in an autophagy-dependent manner and reducing the immunopathological damage mediated by macrophages.

Automated summary

This study revealed that melatonin protects vascular endothelial cells in KD by suppressing cell apoptosis in an autophagy-dependent manner and reducing the immunopathological damage mediated by macrophages.