Abstract
Atherosclerosis (AS) is a chronic inflammatory disease that involves cell death and endothelial dysfunction. Melatonin is an endocrine hormone with anti-inflammatory and anti-AS effects. However, the underlying molecular mechanisms of melatonin anti-AS effect are still unknown. A previous study has shown that pyroptosis plays a detrimental role in AS development. Therefore, this study was designed to investigate the anti-pyroptotic effects and potential mechanisms of melatonin in the atherosclerotic endothelium. In this study, melatonin attenuated the expression of pyroptosis-related genes, including NLRP3, caspase-1 and IL-1β, in human umbilical vein endothelial cells treated with oxidised low-density lipoprotein. Furthermore, melatonin up-regulated ten-eleven translocation 2 (TET2) expression, inhibited ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) methylation and reduced pyroptosis. The up-regulation of UQCRC1 via melatonin improved mitochondrial function, thereby inhibiting oxidative stress and endothelial cell pyroptosis. Collectively, our results indicated that melatonin prevented endothelial cell pyroptosis by up-regulating TET2 to inhibit UQCRC1 methylation and improve mitochondrial function.
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