TMAO promotes vascular endothelial cell pyroptosis via the LPEAT-mitophagy pathway

Trimethylamine N-oxide (TMAO) is a novel risk factor for atherosclerosis, and its underlying regulatory mechanisms are under intensive investigation. Inflammation-related vascular endothelial damage is the major driver in atherogenic process. Pyroptosis, a type of proinflammatory programmed cell dea...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2024-04, Vol.703, p.149667, Article 149667
Main Authors: Chen, Yanmei, Yuan, Chuchu, Qin, Wenhua, Yu, Bo, Wei, Dangheng, Wu, Peng
Format: Article
Language:English
Subjects:
Atherosclerosis
Atherosclerosis - metabolism
Endothelial cell damage
endothelial cells
Endothelial Cells - metabolism
Humans
LPEAT
Methylamines - metabolism
Methylamines - pharmacology
Mitophagy
phosphatidylethanolamines
Pyroptosis
risk factors
TMAO
trimethylamine
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Summary:Trimethylamine N-oxide (TMAO) is a novel risk factor for atherosclerosis, and its underlying regulatory mechanisms are under intensive investigation. Inflammation-related vascular endothelial damage is the major driver in atherogenic process. Pyroptosis, a type of proinflammatory programmed cell death, has been proved to promote the initiation and progression of atherosclerosis. In our study, we found that TMAO triggered endothelial cells excessive mitophagy, thereby facilitating pyroptosis. This process is mediated by the upexpression of phosphatidylethanolamine acyltransferase (LPEAT). These findings provide insights into TMAO-induced vascular endothelial cell damage and suggest that LPEAT may be a valuable target for the prevention and treatment of atherosclerosis. •TMAO leads to endothelial cell mitophagy and pyroptosis.•The mitophagy inhibitor reduces endothelial cell pyroptosis-induced by TMAO.•The upregulation of LPEAT mediated the increased mitophagy and pyroptosis induced by TMAO.
ISSN:0006-291X
1090-2104
1090-2104
DOI:10.1016/j.bbrc.2024.149667