Trimethylamine N‐oxide promotes apoE−/− mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway

2020/02/03 by Peng Wu, Jinna Chen, JinNa Chen +13 · 143 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · Medicine · #Apolipoprotein E #Apoptosis #Biochemistry #Biology #Cancer research #Cell biology #Chemistry #Cholesterol #Downregulation and upregulation #Endothelial stem cell #Foam cell #Heme Oxygenase-1 and Carbon Monoxide #Immune cells in cancer #Inflammasome and immune disorders #Internal medicine #Lipoprotein #Medicine #Oxysterol #Programmed cell death #Pyroptosis #Reactive oxygen species #SDHB

paper · doi:10.1002/jcp.29518

published in Journal of Cellular Physiology 235(10), 6582-6591 (Wiley)

openalex publication_date 2020/02/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/26

Abstract

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.

Cited by

• Nephropathy 1 Formula alleviates kidney injury by ameliorating mitochondrial dysfunction and pyroptosis in diabetic nephropathy through the TMAO-mROS-NLRP3 axis
• Gut Microbiota and Cardiovascular Disease. [europepmc]
• Implication of Gut Microbiota in Cardiovascular Diseases. [europepmc]
• The Role of Gut Bacterial Metabolites in Brain Development, Aging and Disease. [europepmc]
• Pyroptosis in the Initiation and Progression of Atherosclerosis. [europepmc]
• Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease. [europepmc]
• Pyroptosis, metabolism, and tumor immune microenvironment. [europepmc]
• A Bibliometric Analysis of Pyroptosis From 2001 to 2021. [europepmc]
• Pyroptosis: A promising therapeutic target for noninfectious diseases. [europepmc]
• Pyroptosis-Induced Inflammation and Tissue Damage. [europepmc]
• Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis. [europepmc]
• HDAC11 promotes both NLRP3/caspase-1/GSDMD and caspase-3/GSDME pathways causing pyroptosis via ERG in vascular endothelial cells. [europepmc]
• Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms. [europepmc]
• Gut-Flora-Dependent Metabolite Trimethylamine-N-Oxide Promotes Atherosclerosis-Associated Inflammation Responses by Indirect ROS Stimulation and Signaling Involving AMPK and SIRT1. [europepmc]
• NLRP3 Inflammasome/Pyroptosis: A Key Driving Force in Diabetic Cardiomyopathy. [europepmc]
• Aorta- and liver-generated TMAO enhances trained immunity for increased inflammation via ER stress/mitochondrial ROS/glycolysis pathways. [europepmc]
• Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis. [europepmc]
• Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? [europepmc]
• Contribution of Trimethylamine N-Oxide (TMAO) to Chronic Inflammatory and Degenerative Diseases. [europepmc]
• Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder. [europepmc]
• The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review. [europepmc]
• Gut microbiota and microbiota-derived metabolites in cardiovascular diseases. [europepmc]
• Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire. [europepmc]
• Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets. [europepmc]
• ROS induced pyroptosis in inflammatory disease and cancer. [europepmc]
• Gut-X axis. [europepmc]

Related

• Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide
• TrimethylamineN-Oxide, the Microbiome, and Heart and Kidney Disease
• L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE−/− transgenic mice expressing CETP
• Association of moderately elevated trimethylamine N-oxide with cardiovascular risk: is TMAO serving as a marker for hepatic insulin resistance
• The gut microbiota metabolite trimethylamine N-oxide promotes cardiac hypertrophy by activating the autophagic degradation of SERCA2a