Open AccessMicroRNA‐302c‐3p inhibits endothelial cell pyroptosis via directly targeting NOD‐, LRR‐ and pyrin domain‐containing protein 3 in atherosclerosis
Author(s) -
Bai Baochen,
Yang Yanyan,
Ji Shengxiang,
Wang Shizhong,
Peng Xingang,
Tian Chao,
Sun RuiCong,
Yu Tao,
Chu Xianming
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16500
Subject(s) - pyroptosis , inflammasome , pyrin domain , inflammation , nod , gene silencing , caspase 1 , microbiology and biotechnology , microrna , cancer research , immunology , biology , in vivo , gene , biochemistry
Inflammation and endothelial dysfunction are important participants and drivers in atherosclerosis. NOD‐, LRR‐ and pyrin domain‐containing protein 3 (NLRP3) inflammasome activation and the resulting pyroptosis are involved in the initiation and vicious circle of chronic inflammation, thus playing an indispensable role in atherosclerosis. Accordingly, blocking the activation of NLRP3 inflammasome may be a promising treatment strategy to blunt the progression of atherosclerosis. In this study, it was demonstrated that miR‐302c‐3p exerted anti‐pyroptosis effects by directly targeting NLRP3 in vivo and in vitro. In brief, the expression of miR‐302c‐3p was down‐regulated whereas the expression of NLRP3 was up‐regulated in human plaques and in vitro pyroptosis model of endothelial cells. Overexpression of miR‐302c‐3p suppressed endothelial cell pyroptosis by targeting specific sites of NLRP3. By comparison, down‐regulation of endogenous miR‐302c‐3p led to the opposite results, which were reversed by silencing the expression of NLRP3. Finally, the up‐regulation of miR‐302c‐3p inhibited the inflammation and pyroptosis of atherosclerosis mouse model. In conclusion, miR‐302c‐3p may be a powerful and attractive target for suppressing endothelial inflammation and pyroptosis, providing a novel strategy for preventing or alleviating the progression of atherosclerosis.