Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation
Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation
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Sirtuin3 对氧化应激和 NLRP3 炎症小体在 ox-LDL 刺激下胆固醇积累和巨噬细胞泡沫细胞形成中的保护作用
DOI：
10.1016/j.bcp.2021.114665
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发表时间：
2021-07-02
影响因子：
5.8
通讯作者：
Meng, Guoliang
中科院分区：
文献类型：
--
作者：
Ding, Yue;Gong, Weiwei;Meng, Guoliang
Sirtuin 3（SIRT 3）参与活性氧簇（ROS）、细胞代谢、凋亡和炎症。然而，SIRT 3在巨噬细胞中在动脉粥样硬化病理生理过程中的确切作用尚不清楚。本研究旨在探讨SIRT 3对氧化低密度脂蛋白（ox-LDL）刺激的巨噬细胞脂质摄取和泡沫细胞转化的影响及其可能机制。与野生型（WT）小鼠相比，SIRT 3缺陷进一步增加泡沫细胞形成和细胞胆固醇积累，加重氧化应激，损害线粒体通透性，减少视神经萎缩1（OPA 1），但增强动力蛋白相关蛋白1（DRP 1）表达，并促进SIRT 3敲除（KO）小鼠ox-LDL刺激的巨噬细胞中NLR家族pyrin domaincontaining protein 3（NLRP 3）的活化。二氢杨梅素（DMY），一种潜在的化合物，以提高SIRT 3的表达，显着抑制细胞胆固醇积累，抑制泡沫细胞形成，改善线粒体功能，减弱氧化应激，并减轻NLRP 3激活ox-LDL刺激的巨噬细胞。DMY对SIRT 3基因敲除小鼠巨噬细胞的上述保护作用不明显。总之，本研究证实了SIRT 3对氧化应激的保护作用和NLRP 3炎性体在ox-LDL刺激下巨噬细胞胆固醇蓄积和泡沫细胞形成中的作用，为动脉粥样硬化的预防和治疗提供了新的策略。
Sirtuin3 (SIRT3) is involved in reactive oxygen species (ROS), cell metabolism, apoptosis and inflammation. However, the exact role of SIRT3 in macrophages during pathophysiological process of atherosclerosis remains unclear. The present study was to investigate the possible effects and mechanisms of SIRT3 on lipid uptake and foam cells transforming in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages. Compared with wild-type (WT) mice, SIRT3 deficiency further increased foam cell formation and cellular cholesterol accumulation, exacerbated oxidative stress, impaired mitochondrial permeability potential, decreased optic atrophy 1 (OPA1) but enhanced dynamin-related protein 1 (DRP1) expression, and promoted NLR family pyrin domaincontaining protein 3 (NLRP3) activation in ox-LDL-stimulated macrophages from SIRT3 knockout (KO) mice. Dihydromyricetin (DMY), a potential compound to enhance SIRT3 expression, significantly inhibited cellular cholesterol accumulation, suppressed foam cell formation, improved mitochondrial function, attenuated oxidative stress, and alleviated NLRP3 activation in ox-LDL-stimulated macrophages. Moreover, above protective effects of DMY was unavailable in macrophages from SIRT3 KO mice. Collectively, the study demonstrated the protective role of SIRT3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation, which is beneficial to provide novel strategy for atherosclerosis prevention and treatment.