Trimethylamine N‐oxide promotes apoE−/− mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway
Abstract
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.
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Trimethylamine N-oxide has been shown to enhance atherosclerosis in most, but not all, mechanistic and animal model studies.
“TMAO has been shown to enhance atherosclerosis in most, but not all, mechanistic and animal model studies7, 9, 78–82.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [79]
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- Authors
- Wu, P., Chen, J., Chen, J., Tao, J., Wu, S., Xu, G., Wang, Z., Wei, D., & Yin, W.
- Affiliations
- University of South China (CN)
- Hunan YueYang Maternal and Child Medicine Health‐Care Hospital Hunan Province Innovative Training Base for Medical Postgraduates Yueyang Hunan China
- 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
- Corresponding author
- Wei, DangHeng
- Yin, WeiDong
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2020-02-03
- Volume
- 235
- Issue
- 10
- Pages
- 6582-6591
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W3003321487
- Cited by
- 140
- References
- 25
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 20 · 2023: 34 · 2022: 29 · 2021: 17 · 2020: 5
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31870937, 81970389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- trimethylamine N-oxide, atherosclerosis, reactive oxygen species, mitochondrial dysfunction, ApoE-deficient mice, high-fat diet, gut microbiota, cardiovascular risk factors, N-acetylcysteine
- MeSH terms
- Pyroptosis, Animals, Apolipoproteins E, Cells, Cultured, Humans, Methylamines, Mitochondria, Succinate Dehydrogenase, Signal Transduction, Up-Regulation, Reactive Oxygen Species, Atherosclerosis, Mice, Human Umbilical Vein Endothelial Cells
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