{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:05:54Z","timestamp":1789103154479,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL148711"],"award-info":[{"award-number":["R01HL148711"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01HL148711"],"award-info":[{"award-number":["R01HL148711"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["24IPA1276357"],"award-info":[{"award-number":["24IPA1276357"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["24IPA1276357"],"award-info":[{"award-number":["24IPA1276357"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, is a known risk factor for cardiovascular disease. We previously showed that TMAO induces NLRP3 inflammasome activation and contributes to endothelial dysfunction. However, the upstream mechanisms linking TMAO to inflammasome activation and barrier injury remain unclear. In the present study, we examined whether membrane raft (MR) redox signaling contributes to TMAO-induced NLRP3 inflammasome activation and endothelial dysfunction. MR clustering, colocalization of MRs with NADPH oxidase subunits, inflammasome formation, and junction protein expression were assessed by Western blot analysis. RT-qPCR was performed to further assess the mRNA expression of junctional genes. Superoxide production was measured by electron spin resonance (ESR), caspase-1 activity was determined using a biochemical assay kit, IL-1\u03b2 production was measured by ELISA, and endothelial permeability was evaluated using an FITC-dextran assay. TMAO increased MR clustering in endothelial cells in a dose-dependent manner. TMAO also enhanced the colocalization of MRs with p47phox and gp91phox, indicating the formation of an MR-associated redox signaling axis. In addition, TMAO increased superoxide production; promoted NLRP3 inflammasome formation; elevated caspase-1 activity and IL-1\u03b2 production; reduced the expression of ZO-2, ZO-1, VE cadherin and occludin; and increased endothelial permeability. Pretreatment with the MR disruptor MCD, the NADPH oxidase inhibitor DPI, or the caspase-1 inhibitor WEHD significantly attenuated these TMAO-induced effects. These findings demonstrate that TMAO-mediated endothelial injury is dependent on the MR-associated redox signaling axis. TMAO promotes MR-associated redox signaling, leading to NADPH oxidase activation, superoxide generation, NLRP3 inflammasome activation, disruption of endothelial junction proteins, and barrier dysfunction. Targeting MR-associated signaling pathways may offer a novel therapeutic strategy to mitigate TMAO-induced vascular inflammation and endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/antiox15091138","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:05:43Z","timestamp":1788941143000},"page":"1138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Membrane Raft Redox Signaling Mediates Trimethylamine N-Oxide-Induced NLRP3 Inflammasome Activation and Endothelial Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-6345","authenticated-orcid":false,"given":"Md Areeful","family":"Haque","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mohammad Atiqur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Inavolu Sriram","family":"Sandeep","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Sindhura","family":"Pasham","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Sayantap","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4284-0780","authenticated-orcid":false,"given":"Krishna M.","family":"Boini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-2495","authenticated-orcid":false,"given":"Saisudha","family":"Koka","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.2174\/1874192401004010302","article-title":"The endothelium and its role in regulating vascular tone","volume":"4","author":"Sandoo","year":"2010","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nri2171","article-title":"Evolving functions of endothelial cells in inflammation","volume":"7","author":"Pober","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Medina-Leyte, D.J., Zepeda-Garc\u00eda, O., Dom\u00ednguez-P\u00e9rez, M., Gonz\u00e1lez-Garrido, A., Villarreal-Molina, T., and Jacobo-Albavera, L. (2021). Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083850"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41419-020-02985-x","article-title":"NLRP3 inflammasome in endothelial dysfunction","volume":"11","author":"Bai","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhen, J., Zhou, Z., He, M., Han, H.X., Lv, E.H., Wen, P.B., Liu, X., Wang, Y.T., Cai, X.C., and Tian, J.Q. (2023). The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1085041"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.1172\/JCI72331","article-title":"The contributory role of gut microbiota in cardiovascular disease","volume":"124","author":"Tang","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shanmugham, M., Bellanger, S., and Leo, C.H. (2023). Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040504"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Eyileten, C., Jarosz-Popek, J., Jakubik, D., Gasecka, A., Wolska, M., Ufnal, M., Postula, M., Toma, A., Lang, I.M., and Siller-Matula, J.M. (2021). Plasma Trimethylamine-N-Oxide Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.728724"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, B., Qiu, J., Lian, J., Yang, X., and Zhou, J. (2021). Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.723886"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4634172","DOI":"10.1155\/2020\/4634172","article-title":"Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis","volume":"2020","author":"Liu","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"936","DOI":"10.17305\/bb.2023.8893","article-title":"The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review","volume":"23","author":"Oktaviono","year":"2023","journal-title":"Biomol. Biomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2016.02.011","article-title":"Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk","volume":"165","author":"Zhu","year":"2016","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1161\/ATVBAHA.107.159772","article-title":"Critical role of lipid raft redox signaling platforms in endostatin-induced coronary endothelial dysfunction","volume":"28","author":"Jin","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1089\/ars.2010.3619","article-title":"Lipid raft redox signaling: Molecular mechanisms in health and disease","volume":"15","author":"Jin","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1089\/ars.2008.2220","article-title":"NADPH oxidase-dependent signaling in endothelial cells: Role in physiology and pathophysiology","volume":"11","author":"Frey","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1161\/01.RES.87.10.840","article-title":"Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress","volume":"87","author":"Cai","year":"2000","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/cmi.2014.89","article-title":"NADPH oxidases: An overview from structure to innate immunity-associated pathologies","volume":"12","author":"Panday","year":"2015","journal-title":"Cell. Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s11658-023-00462-9","article-title":"The NLRP3 inflammasome: Contributions to inflammation-related diseases","volume":"28","author":"Chen","year":"2023","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Blevins, H.M., Xu, Y., Biby, S., and Zhang, S. (2022). The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.879021"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","article-title":"The inflammasomes","volume":"140","author":"Schroder","year":"2010","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1159\/000484623","article-title":"Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction","volume":"44","author":"Boini","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Marques-da-Silva, D., and Lagoa, R. (2023). Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants\u2019 Cellular Effects. Molecules, 28.","DOI":"10.3390\/molecules28186598"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and tumor progression: Signaling pathways and targeted intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Singh, G.B., Zhang, Y., Boini, K.M., and Koka, S. (2019). High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143570"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.bbamcr.2014.01.033","article-title":"Activation of inflammasomes in podocyte injury of mice on the high fat diet: Effects of ASC gene deletion and silencing","volume":"1843","author":"Boini","year":"2014","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbamcr.2014.11.012","article-title":"Endothelial Nlrp3 inflammasome activation associated with lysosomal destabilization during coronary arteritis","volume":"1853","author":"Chen","year":"2015","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, Y., Xia, M., Gulbins, E., Boini, K.M., and Li, P.L. (2014). Activation of Nlrp3 inflammasomes enhances macrophage lipid-deposition and migration: Implication of a novel role of inflammasome in atherogenesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087552"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12738","DOI":"10.18632\/aging.205243","article-title":"Contribution of membrane raft redox signalling to visfatin-induced inflammasome activation and podocyte injury","volume":"15","author":"Koka","year":"2023","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1261\/rna.079799.123","article-title":"LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function","volume":"30","author":"Lewis","year":"2024","journal-title":"RNA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1093\/nar\/gkw095","article-title":"Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor","volume":"44","author":"Macia","year":"2016","journal-title":"Nucleic. Acids. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41423-021-00670-3","article-title":"An update on the regulatory mechanisms of NLRP3 inflammasome activation","volume":"18","author":"Paik","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gora, I.M., Ciechanowska, A., and Ladyzynski, P. (2021). NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes. Cells, 10.","DOI":"10.3390\/cells10020314"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41392-023-01687-y","article-title":"The role of inflammasomes in human diseases and their potential as therapeutic targets","volume":"9","author":"Yao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jarmukhanov, Z., Mukhanbetzhanov, N., Kozhakhmetov, S., Nurgaziyev, M., Sailybayeva, A., Bekbossynova, M., and Kushugulova, A. (2024). The association between the gut microbiota metabolite trimethylamine N-oxide and heart failure. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1440241"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Canyelles, M., Borr\u00e0s, C., Rotllan, N., Tondo, M., Escol\u00e0-Gil, J.C., and Blanco-Vaca, F. (2023). Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031940"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.trsl.2020.08.007","article-title":"TMAO: How gut microbiota contributes to heart failure","volume":"228","author":"Zhang","year":"2021","journal-title":"Transl. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1161\/CIRCRESAHA.118.313237","article-title":"Emerging Roles of Vascular Endothelium in Metabolic Homeostasis","volume":"123","author":"Pi","year":"2018","journal-title":"Circ. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1161\/CIRCRESAHA.116.306534","article-title":"Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability","volume":"120","author":"Komarova","year":"2017","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/nyas.14798","article-title":"Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival","volume":"1514","author":"Kuo","year":"2022","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1154641","DOI":"10.1080\/21688370.2016.1154641","article-title":"Junctional proteins of the blood-brain barrier: New insights into function and dysfunction","volume":"4","author":"Stamatovic","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1996830","DOI":"10.1080\/21688370.2021.1996830","article-title":"Epithelial integrity; junctional complexes, and biomarkers associated with intestinal functions","volume":"10","author":"Alizadeh","year":"2022","journal-title":"Tissue Barriers"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Duong, C.N., and Vestweber, D. (2020). Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00519"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.7150\/ijbs.7502","article-title":"The vascular endothelium and human diseases","volume":"9","author":"Rajendran","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1038\/sj.cdd.4401451","article-title":"Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease","volume":"11","author":"Austin","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease","volume":"116","author":"Tang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1681\/ASN.2014111063","article-title":"Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden","volume":"27","author":"Stubbs","year":"2015","journal-title":"J. Am. Soc. Nephrol. 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