Trimethylamine N-oxide promotes apoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway

被引：135

作者：

Wu, Peng ^{[1
,2
,3
]}

Chen, JinNa ^{[1
,2
]}

Chen, JiaoJiao ^{[1
,2
]}

Tao, Jun ^{[1
,2
]}

Wu, ShiYuan ^{[3
]}

Xu, GaoSheng ^{[3
]}

Wang, Zuo ^{[1
,2
]}

Wei, DangHeng ^{[1
,2
]}

Yin, WeiDong ^{[1
,2
]}

机构：

[1] Univ South China, Hunan Int Sci & Technol Cooperat Base Arterioscle, Hunan Prov Innovat Training Base Med Postgrad, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang, Hunan, Peoples R China

[2] Univ South China, Yueyang Woman & Childrens Med Ctr, Hengyang Med Coll, Hengyang, Hunan, Peoples R China

[3] Hunan YueYang Maternal & Child Med Health Care Ho, Hunan Prov Innovat Training Base Med Postgrad, Yueyang, Hunan, Peoples R China

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2020年 / 235卷 / 10期

基金：

中国国家自然科学基金;

关键词：

atherosclerosis; pyroptosis; ROS; SDHB; TMAO; INFLAMMATION; ACTIVATION;

D O I：

10.1002/jcp.29518

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Trimethylamine N-oxide (TMAO) is produced from the phosphatidylcholine metabolism of gut flora and acts as a risk factor of cardiovascular disease. However, the underlying mechanisms for its proatherogenic action remain unclear. This study aimed to observe the effect of TMAO on endothelial cell pyroptosis and explore the underlying mechanisms. Our results showed that TMAO promoted the progression of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice fed a high-fat diet. Pyroptosis and succinate dehydrogenase complex subunit B (SDHB) upregulation were detected in the vascular endothelial cells of apoE(-/-) mice and in cultured human umbilical vein endothelial cells (HUVECs) treated with TMAO. Overexpression of SDHB in HUVECs enhanced pyroptosis and impaired mitochondria and high reactive oxygen species (ROS) level. Pyroptosis in the SDHB overexpression of endothelial cells was inhibited by the ROS scavenger NAC. In summary, TMAO promotes vascular endothelial cell pyroptosis via ROS induced through SDHB upregulation, thereby contributing to the progression of atherosclerotic lesions.

引用

页码：6582 / 6591

页数：10

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