The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-κB (Nuclear Factor κB) Signals
Open accessAbstract
Objectives: Vascular calcification is highly prevalent in patients with chronic kidney disease. Increased plasma trimethylamine N-oxide (TMAO), a gut microbiota-dependent product, concentrations are found in patients undergoing hemodialysis. However, a clear mechanistic link between TMAO and vascular calcification is not yet established. In this study, we investigate whether TMAO participates in the progression of vascular calcification using in vitro, ex vivo, and in vivo models. Approach and Results: Alizarin red staining revealed that TMAO promoted calcium/phosphate-induced calcification of rat and human vascular smooth muscle cells in a dose-dependent manner, and this was confirmed by calcium content assay. Similarly, TMAO upregulated the expression of bone-related molecules including Runx2 (Runt-related transcription factor 2) and BMP2 (bone morphogenetic protein-2), suggesting that TMAO promoted osteogenic differentiation of vascular smooth muscle cells. In addition, ex vivo study also showed the positive regulatory effect of TMAO on vascular calcification. Furthermore, we found that TMAO accelerated vascular calcification in rats with chronic kidney disease, as indicated by Mico-computed tomography analysis, alizarin red staining and calcium content assay. By contrast, reducing TMAO levels by antibiotics attenuated vascular calcification in chronic kidney disease rats. Interestingly, TMAO activated NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and NF-κB (nuclear factor κB) signals during vascular calcification. Inhibition of NLRP3 inflammasome and NF-κB signals attenuated TMAO-induced vascular smooth muscle cell calcification. Conclusions: This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-κB signals, suggesting the potential link between gut microbial metabolism and vascular calcification. Reducing the levels of TMAO could become a potential treatment strategy for vascular calcification in chronic kidney disease.
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“It has also been shown to promote platelet reactivity and thrombosis potential14, 83–85, vascular inflammation and inflammasome activation86–88, heightened heart failure89–91 and CKD92–95 related phenotypes in animal models (Figure 2).”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [88]
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Gut microbiota and cardiovascular disease.
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Metadata
- Authors
- Zhang, X., Li, Y., Yang, P., Liu, X., Lu, L., Chen, Y., Zhong, X., Li, Z., Liu, H., Ou, C., Yan, J., & Chen, M.
- Affiliations
- Zhujiang Hospital (CN)
- Sun Yat-sen University (CN)
- Corresponding author
- Zhang, Xiuli
- Li, Yining
- Yang, Pingzhen
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2020-03
- Volume
- 40
- Issue
- 3
- Pages
- 751-765
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2999495572
- Cited by
- 291
- References
- 59
- Citations by year
- 2026: 45 · 2025: 60 · 2024: 53 · 2023: 42 · 2022: 46 · 2021: 32 · 2020: 13
- FWCI
- 20.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81870190, U1501222, 31771060, 81871504, 81770280)
- Science and Technology Planning Project of Guangdong Province (2017A020215184)
- Basic and Applied Basic Research Foundation of Guangdong Province (2019A1515010682)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- trimethylamine N-oxide, vascular calcification, NLRP3 inflammasome, NF-κB signaling, chronic kidney disease, vascular smooth muscle cells, osteogenic differentiation, Runx2, BMP-2, gut microbiota, antibiotics, hemodialysis
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adult, Aged, Animals, Anti-Bacterial Agents, Aorta, Thoracic, Cells, Cultured, Disease Models, Animal, Female, Humans, Male, Methylamines, Middle Aged, Muscle, Smooth, Vascular, Osteogenesis, Signal Transduction, NF-kappa B, Tibial Arteries, Myocytes, Smooth Muscle, Tissue Culture Techniques, Renal Insufficiency, Chronic, Inflammasomes, Vascular Calcification
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