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In this study, we used apoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice fed with high-fat diet for 12\u00a0weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48\u00a0h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root\u00a0of apoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice. MCC950 inhibited the activation of NLRP3\/ASC\/Caspase-1\/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1\u03b2 and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.<\/jats:p>","DOI":"10.1038\/s41598-021-98437-3","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T10:21:04Z","timestamp":1632910864000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":193,"title":["The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages"],"prefix":"10.1038","volume":"11","author":[{"given":"Wenyun","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danbin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Suo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"issue":"1","key":"98437_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1080\/1744666X.2020.1860757","volume":"17","author":"R Truong","year":"2021","unstructured":"Truong, R. et al. 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