Work

TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE−/− mice via MBOAT2-mediated endoplasmic reticulum stress

Year: 2024

Type: article

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 .

Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

DOI: 10.1016/j.bbalip.2024.159559