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• W2893567108 abstract "Background This study aimed at investigating whether NLRP 3 (the Nod like receptor family, pyrin domain‐containing 3 protein) inflammasome activation induced HMGB 1 (high mobility group box‐1 protein) secretion and foam cell formation in human vascular smooth muscle cells ( VSMC s) and atherosclerosis in ApoE −/− mice. Methods and Results VSMC s or ApoE −/− mice were treated with lipopolysaccharides ( LPS ) and/or ATP or LPS and high‐fat diet to induce NLRP 3 inflammasome activation. HMGB 1 distribution and foam cell formation in VSMC s were characterized. Liver X receptor α and ATP ‐binding cassette transporter expression were determined. The impact of NLRP 3 or receptor for advanced glycation end product silencing, ZYVAD ‐ FMK (caspase‐1 inhibitor), glycyrrhizin ( HMGB 1 inhibitor) or receptor for advanced glycation end product antagonist peptide on HMGB 1 secretion, foam cell formation, liver X receptor α and ATP ‐binding cassette transporter expression was examined. Expression level of HMGB 1 in human atherosclerosis obliterans arterial tissues was characterized. Our results found that NLRP 3 inflammasome activation promoted foam cell formation and HMGB 1 secretion in VSMC s. Extracellular HMGB 1 was a key signal molecule in inflammasome activation‐mediated foam cell formation. Furthermore, inflammasome activation‐induced HMGB 1 activity and foam cell formation were achieved by receptor for advanced glycation end product/liver X receptor α / ATP ‐binding cassette transporter glycyrrhizin. Experiments in vivo found glycyrrhizin significantly attenuated the LPS /high‐fat diet‐induced atherosclerosis and serum HMGB 1 levels in mice. Finally, levels of HMGB 1 and NLRP 3 were increased in tunica media adjacent to intima of atherosclerosis obliteran arteries. Conclusions Our results revealed that HMGB1 is a key downstream signal molecule of NLRP 3 inflammasome activation and plays an important role in VSMC s foam cell formation and atherogenesis by downregulating liver X receptor α and ATP ‐binding cassette transporter expression through receptor for advanced glycation end product." @default.
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• W2893567108 date "2018-10-02" @default.
• W2893567108 modified "2023-10-15" @default.
• W2893567108 title "Activation of NLRP3 Inflammasome Promotes Foam Cell Formation in Vascular Smooth Muscle Cells and Atherogenesis Via HMGB1" @default.
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• W2893567108 doi "https://doi.org/10.1161/jaha.118.008596" @default.
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