Trimethylamine N-oxide promotes apoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway
Trimethylamine N-oxide promotes apoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway
复制标题
N-氧化三甲胺通过SDHB/ROS途径诱导血管内皮细胞焦亡，促进apoE∧/∪小鼠动脉粥样硬化
DOI：
10.1002/jcp.29518
复制
发表时间：
2020-02-03
影响因子：
5.6
通讯作者：
Yin, WeiDong
中科院分区：
文献类型：
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作者：
Wu, Peng;Chen, JinNa;Yin, WeiDong
氧化三甲胺（TMAO）是由肠道植物群的磷脂酰胆碱代谢产生的，是心血管疾病的危险因素。然而，其致动脉粥样硬化作用的潜在机制仍不清楚。本研究旨在观察氧化三甲胺对内皮细胞凋亡的影响，并探讨其作用机制。我们的研究结果表明，TMAO促进了高脂饮食喂养的载脂蛋白E缺陷（apoE（-/-））小鼠动脉粥样硬化病变的进展。在apoE（-/-）小鼠血管内皮细胞和培养的人脐静脉内皮细胞（HUVECs）中检测到TMAO处理的焦亡和琥珀酸脱氢酶复合物亚单位B（SDHB）上调。SDHB在HUVECs中的过表达增强了细胞凋亡，损伤了线粒体和高活性氧（ROS）水平。ROS清除剂NAC可抑制SDHB过度表达的内皮细胞中的焦亡。总之，TMAO通过SDHB上调诱导的ROS促进血管内皮细胞焦亡，从而促进动脉粥样硬化病变的进展。
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.