Bo Yu , Chuchu Yuan , Jinna Chen , Zhixiang Zhou , Yile Zhang , Ming Su , Dangheng Wei , Peng Wu
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引用次数: 0
Abstract
Trimethylamine N-oxide (TMAO), a metabolite produced by intestinal flora, is recognized as an independent risk factor for atherosclerosis and atherosclerotic cardiovascular diseases. However, the underlying mechanism remains poorly understood. Here, we showed that dietary TMAO supplementation accelerates atherosclerosis in ApoE−/− mice. Pyroptosis and the expression of phospholipid-modifying enzyme MBOAT2 were increased in endothelial cells within atherosclerotic lesions. Genetic upregulation of MBOAT2 via adeno-associated virus with endothelium-specific promoter results in increased atherosclerotic lesions in ApoE−/− mice. Mechanistically, the overexpression of MBOAT2 disrupted glycerophospholipid metabolism and induced endothelial cell pyroptosis in an Endoplasmic reticulum stress-dependent manner. These data reveal that TMAO promotes endothelial cell pyroptosis and the progression of atherosclerotic lesions through the upregulation of MBOAT2, indicating that MBOAT2 is a promising therapeutic target for atherosclerosis.
期刊介绍:
BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.