{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:39:11Z","timestamp":1791689951892,"version":"4.3.4"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>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-\u03baB (nuclear factor \u03baB) signals during vascular calcification. Inhibition of NLRP3 inflammasome and NF-\u03baB signals attenuated TMAO-induced vascular smooth muscle cell calcification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-\u03baB 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.119.313414","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T05:00:19Z","timestamp":1579150819000},"page":"751-765","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":281,"title":["Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-\u03baB (Nuclear Factor \u03baB) Signals"],"prefix":"10.1161","volume":"40","author":[{"given":"Xiuli","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, China (X.Z., Y.L., P.Y., X.L., X.Z., Z.L., H.L., C.O., J.Y., 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