2. Academic Validation
  3. TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE-/- mice via MBOAT2-mediated endoplasmic reticulum stress

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

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Dec;1869(8):159559. doi: 10.1016/j.bbalip.2024.159559.
Bo Yu 1,  Chuchu Yuan 1,  Jinna Chen 1,  Zhixiang Zhou 1,  Yile Zhang 1,  Ming Su 1,  Dangheng Wei 2,  Peng Wu 3
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
  • 2 Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address: weizhonghua99@126.com.
  • 3 Hengyang Maternal and Child Health Hospital, Hengyang 421001, Hunan Province, China. Electronic address: 905595479@qq.com.
PMID: 39179098 DOI: 10.1016/j.bbalip.2024.159559
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.

Keywords

Atherosclerosis; Endoplasmic reticulum stress; Endothelial cell; MBOAT2; Pyroptosis; TMAO.

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