Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation

[Display omitted] 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 effect...

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Bibliographic Details
Published in:Biochemical pharmacology 2021-10, Vol.192, p.114665-114665, Article 114665
Main Authors: Ding, Yue, Gong, Weiwei, Zhang, Shuping, Shen, Jieru, Liu, Xiao, Wang, Yuqin, Chen, Yun, Meng, Guoliang
Format: Article
Language:English
Subjects:
Inflammation
Macrophages
Oxidative stress
Oxidized low-density lipoprotein
Sirtuin3
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Summary:[Display omitted] 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 domain-containing 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.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2021.114665