Trimethylamine N-oxide promotes tissue factor expression and activity in vascular endothelial cells: A new link between trimethylamine N-oxide and atherosclerotic thrombosis
Abstract
Trimethylamine-N-oxide (TMAO), one of the products in choline metabolite, is recently reported to be associated with cardiovascular diseases (CVD) that mainly attribute to atherothrombosis. However, the mechanisms how TMAO functions in the pathogenesis of CVD and atherothrombosis remain elusive. Tissue factor (TF) has been implicated in the thrombogenicity of atherosclerotic plaques. In the present study, we demonstrated that TMAO promoted TF (but not TF pathway inhibitor) expression via activation of NF-κB signaling pathway in primary human coronary artery endothelial cells (HCAECs). TMAO strongly increased TF activity and thrombin production. Further, a small dose of TMAO significantly increased TF expression and nuclear translocation of NF-κB with the synergistic action of low-dose of pro-atherosclerotic factors, such as TNF-α and HMGB1. Importantly, plasma TMAO level was positively correlated with TF activity in patients with ST-elevation myocardial infarction (STEMI). Altogether, our data revealed that TMAO promoted thrombosis through increasing TF expression and activity. The understanding of the new link between TMAO and atherothrombosis may facilitate therapeutic strategy in the prevention and treatment of atherothrombosis.
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Trimethylamine N-oxide induces expression of tissue factor, the initiator of the extrinsic clotting cascade, in endothelial cells in vitro.
“Recent studies have shown that beyond impacting platelet function, TMAO induces expression of tissue factor (TF), the initiator of the extrinsic clotting, in endothelial cells in vitro122.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [122]
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Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
- Authors
- Cheng, X., Qiu, X., Liu, Y., Yuan, C., & Yang, X.
- Affiliations
- Central South University (CN)
- Corresponding author
- Yang, Xinyu
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 177
- Pages
- 110-116
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W2917538340
- Cited by
- 90
- References
- 33
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 18 · 2023: 13 · 2022: 10 · 2021: 13 · 2020: 9 · 2019: 2
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health and Family Planning Commission of Hunan Province (A2016005)
- National Science Foundation (81602735)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- trimethylamine N-oxide, tissue factor, atherothrombosis, NF-κB signaling, vascular endothelial cells, coronary artery endothelial cells, thrombin generation, TNF-α, HMGB1, ST-elevation myocardial infarction, choline metabolites, cardiovascular disease
- MeSH terms
- Aged, Cells, Cultured, Female, Humans, Male, Methylamines, Middle Aged, Thrombin, Thromboplastin, Thrombosis, Endothelial Cells, Atherosclerosis
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