Evidence map›Paper›PMID 26903003›Full record

ArticleJournal of the American Heart Association2016

Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-κB.

Marcus M Seldin, Yonghong Meng, Hongxiu Qi, WeiFei Zhu, Zeneng Wang, Stanley L Hazen, Aldons J Lusis, Diana M Shih

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 543 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
543citing papers in PubMed, 6 pooled it
30.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

543 citing papers in PubMed, 6 syntheses or guidelines pooled it, 847 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Gut microbes · 2026
    Review
  10. Review
  11. Review
  12. Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. The gut-heart axis in cardio-oncology.Cardiovascular research · 2026
    Review
  19. Review
  20. Article

483 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Marcus M SeldinDepartment of Medicine, Cardiology Division at the University of California, Los Angeles, CA.
Yonghong MengDepartment of Medicine, Cardiology Division at the University of California, Los Angeles, CA.
Hongxiu QiDepartment of Medicine, Cardiology Division at the University of California, Los Angeles, CA.
WeiFei ZhuDepartment of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH.
Zeneng WangDepartment of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH.
Stanley L HazenDepartment of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, OH.
Aldons J LusisDepartment of Medicine, Cardiology Division at the University of California, Los Angeles, CA.
Diana M ShihDepartment of Medicine, Cardiology Division at the University of California, Los Angeles, CA dshih@mednet.ucla.edu.
University of California, Los Angeles · USCleveland Clinic · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
Functional Cardio-MetabolomicsP20HL113452 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2012 to 2016
$4.8M
Dietary Choline, Gut Microbiota, and Susceptibility for Chronic Kidney DiseaseR01DK106000 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2015 to 2018
$2.8M
NHLBI NIH HHS 2 P01 HL030568-31A1NHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS P01 HL030568NHLBI NIH HHS P20HL113452NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01HL103866NHLBI NIH HHS R01 HL103866 06A1NHLBI NIH HHS T32HL69766NIDDK NIH HHS R01 DK106000
6 · The paper itself

Abstract

backgroundThe choline-derived metabolite trimethylamine N-oxide (TMAO) has been demonstrated to contribute to atherosclerosis and is associated with coronary artery disease risk. METHODS AND

resultsWe explored the impact of TMAO on endothelial and smooth muscle cell function in vivo, focusing on disease-relevant outcomes for atherogenesis. Initially, we observed that aortas of LDLR(-/-) mice fed a choline diet showed elevated inflammatory gene expression compared with controls. Acute TMAO injection at physiological levels was sufficient to induce the same inflammatory markers and activate the well-known mitogen-activated protein kinase, extracellular signal-related kinase, and nuclear factor-κB signaling cascade. These observations were recapitulated in primary human aortic endothelial cells and vascular smooth muscle cells. We also found that TMAO promotes recruitment of activated leukocytes to endothelial cells. Through pharmacological inhibition, we further showed that activation of nuclear factor-κB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes.

conclusionsOur results suggest a likely contributory mechanism for TMAO-dependent enhancement in atherosclerosis and cardiovascular risks.

Indexed as

AnimalsAortaAortitisAtherosclerosisCell AdhesionCells, CulturedCholineCoculture TechniquesDisease Models, AnimalEndothelial CellsEnzyme ActivationFemaleGene Expression RegulationGenetic Predisposition to DiseaseHumansLeukocytesCholineMethylaminesMitogen-Activated Protein KinasesNF-kappa BReceptors, LDLtrimethyloxamineatherosclerosiscardiovascular diseaseendothelial cellinflammationleukocyte adhesionnuclear factor‐κB signalingtrimethylamine N‐oxidevascular smooth muscle cell

Identifiers

PMID26903003
PMCPMC4802459
OpenAlexW2288501492

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.