Premium
Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR‐223/NLRP3 axis
Author(s) -
Zhang Yong,
Liu Xin,
Bai Xue,
Lin Yuan,
Li Zhange,
Fu Jiangbo,
Li Mingqi,
Zhao Tong,
Yang Huan,
Xu Ranchen,
Li Jiamin,
Ju Jin,
Cai Benzhi,
Xu Chaoqian,
Yang Baofeng
Publication year - 2018
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12449
Subject(s) - pyroptosis , melatonin , endothelial stem cell , endothelium , gene knockdown , endothelial dysfunction , biology , microbiology and biotechnology , medicine , endocrinology , immunology , inflammation , apoptosis , inflammasome , biochemistry , in vitro
Atherosclerosis ( AS ) is an inflammatory disease linked to endothelial dysfunction. Melatonin is reported to possess substantial anti‐inflammatory properties, which has proven to be effective in AS . Emerging literature suggests that pyroptosis plays a critical role during AS progression. However, whether pyroptosis contributes to endothelial dysfunction and the underlying molecular mechanisms remained unexploited. This study was designed to investigate the antipyroptotic 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 NLRP 3, ASC , cleaved caspase1, NF ‐κB/ GSDMD , GSDMD N‐termini, IL ‐1β, and IL ‐18 in aortic endothelium of melatonin‐treated animals. Consistent antipyroptotic effects were also observed in ox‐ LDL ‐treated human aortic endothelial cells ( HAEC s). We found that lnc RNA MEG 3 enhanced pyroptosis in HAEC s. Moreover, MEG 3 acted as an endogenous sponge by sequence complementarity to suppress the function of miR‐223 and to increase NLRP 3 expression and enhance endothelial cell pyroptosis. Furthermore, knockdown of miR‐223 blocked the antipyroptotic actions of melatonin in ox‐ LDL ‐treated HAEC s. Together, our results suggest that melatonin prevents endothelial cell pyroptosis via MEG 3/miR‐223/ NLRP 3 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.