Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome
Abstract
Recent research demonstrates that the choline-derived metabolite trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis and cardiovascular risks. The NLRP3 inflammasome responds to exogenous and endogenous danger signals involved in the development of atherosclerosis. Moreover, thioredoxin-interactive protein (TXNIP) activation is a key event linked to NLRP3 inflammasome via reactive oxygen species (ROS). Whether TMAO prime NLRP3 inflammasome via ROS-TXNIP pathway remains unclear. This study observed the expression of TXNIP-NLRP3 inflammasome stimulated by TMAO in human umbilical vein endothelial cells (HUVECs), aiming to elucidate the mechanism by which the TMAO may contribute to inflammation and endothelial dysfunction. Our data showed that TMAO significantly triggered oxidative stress and activated TXNIP-NLRP3 inflammasome whereat inflammatory cytokines interleukin (IL)-1β and IL-18 were released in a dose- and time-dependent manner, but endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were inhibited. Moreover, TMAO-mediated effects were observably reversed by ROS inhibitor N-acetylcysteine (NAC) treatment or siRNA-mediated knockdown TXPIN and NLRP3. Taken together, our results firstly reveal that TMAO induces inflammation and endothelial dysfunction via activating ROS-TXNIP-NLRP3 inflammasome, suggest a likely mechanism for TMAO-dependent enhancement in atherosclerosis and cardiovascular risks.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is convincing evidence suggesting an association between TMAO and inflammation.
“nowadays there is convincing evidence suggesting an association between TMAO and inflammation [8,9,10,11,12]”
From Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target (2018) · cites this paper as [11]
TMAO can impact inflammation via priming and activation of the NLRP3 inflammasome in endothelial cells and the arterial vascular wall in mice, involving mitochondrial ROS production, TXNIP, and lysosomal destabilization.
“Recent investigations have suggested TMAO can impact inflammation via priming and activation of the NLRP3 inflammasome in endothelial cells, as well as the arterial vascular wall in mice, involving mitochondrial reactive oxygen species (ROS) production, thioredoxin interacting protein (TXNIP) and lysosomal destabilization87, 130, 131.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [131]
The citation lists haven’t been fetched yet
References 32 · Cited by 507
- Authors
- Sun, X., Jiao, X., Ma, Y., Liu, Y., Zhang, L., He, Y., & Chen, Y.
- Affiliations
- Macau University of Science and Technology (MO)
- Affiliated Hospital of Qingdao University (CN)
- Southwest Medical University (CN)
- Qingdao Municipal Hospital (CN)
- Corresponding author
- He, Yanzheng
- Chen, Yunhui
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 481
- Issue
- 1-2
- Pages
- 63-70
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2550560946
- Cited by
- 507
- References
- 32
- Citations by year
- 2026: 48 · 2025: 63 · 2024: 65 · 2023: 79 · 2022: 65 · 2021: 63 · 2020: 53 · 2019: 19 · 2018: 30 · 2017: 22
- FWCI
- 12.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sichuan Medical Association Fund of China (Q15043)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- trimethylamine N-oxide, NLRP3 inflammasome, TXNIP, reactive oxygen species, endothelial dysfunction, inflammation, human umbilical vein endothelial cells, oxidative stress, IL-1β, IL-18, endothelial nitric oxide synthase, nitric oxide, atherosclerosis, cardiovascular risk, N-acetylcysteine
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Carrier Proteins, Cells, Cultured, Dose-Response Relationship, Drug, Endothelium, Vascular, Humans, Inflammation, Methylamines, Reactive Oxygen Species, Inflammasomes, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
