Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hunan Province Innovative Training Base for Medical Postgraduate, University of South China and Yueyang Woman & Children's Medical Center, Hengyang Medical College, University of South China, Hengyang, Hunan, China.
Hunan YueYang Maternal and Child Medicine Health-Care Hospital, Hunan Province Innovative Training Base for Medical Postgraduates, Yueyang, Hunan, China.
J Cell Physiol. 2020 Oct;235(10):6582-6591. doi: 10.1002/jcp.29518. Epub 2020 Feb 3.
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.
三甲基胺 N-氧化物（TMAO）是肠道菌群磷脂酰胆碱代谢的产物，可作为心血管疾病的危险因素。然而，其促动脉粥样硬化作用的潜在机制尚不清楚。本研究旨在观察 TMAO 对血管内皮细胞细胞焦亡的影响，并探讨其潜在机制。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。apoE 小鼠血管内皮细胞和 TMAO 处理的人脐静脉内皮细胞（HUVEC）中检测到细胞焦亡和琥珀酸脱氢酶复合体亚基 B（SDHB）的上调。在 HUVEC 中转染 SDHB 过表达可增强细胞焦亡并损害线粒体和高活性氧（ROS）水平。ROS 清除剂 NAC 可抑制内皮细胞中 SDHB 过表达诱导的细胞焦亡。总之，TMAO 通过 SDHB 上调诱导的 ROS 促进血管内皮细胞细胞焦亡，从而促进动脉粥样硬化病变的进展。
