Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR ‐223/NLRP3 axis

This study was designed to investigate the anti‐pyroptotic effects of melatonin in atherosclerotic endothelium and to elucidate the potential mechanisms. In this study, high fat diet (HFD) treated ApoE‐/‐ mice were used as an atherosclerotic animal model. We found intragastric administration of melatonin for 12 weeks markedly reduced the atherosclerotic plaque in aorta. Meanwhile, melatonin also attenuated the expression of pyroptosis‐related genes, including NLRP3, ASC, cleaved‐caspase1, NF‐κB/GSDMD, GSDMD‐N termini, IL‐1β, and IL‐18 in aortic endothelium of melatonin‐treated animals. Consistent anti‐pyroptotic effects were also observed in ox‐LDL‐treated human aortic endothelial cells (HAECs). We found that lncRNA MEG3 enhanced pyroptosis in HAECs. Moreover, MEG3 acted as an endogenous sponge by sequence complementarity to suppress the function of miR‐223 and to increase NLRP3 expression and enhance endothelial cell pyroptosis. Furthermore, knockdown of miR‐223 blocked the anti‐pyroptotic actions of melatonin in ox‐LDL‐treated HAECs. Together, our results suggest that melatonin prevents endothelial cell pyroptosis via MEG3/miR‐223/NLRP3 axis in atherosclerosis and therefore melatonin replacement might be considered a new strategy for protecting endothelium against pyroptosis thereby for the treatment of atherosclerosis associated with pyroptosis. This article is protected by copyright. All rights reserved.
Source: Journal of Pineal Research - Category: Research Authors: Tags: Original Article Source Type: research