Evidence map›Paper›PMID 29981269›Full record

ArticleJournal of thrombosis and haemostasis : JTH2018

Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N-oxide-generating pathway, modulates platelet responsiveness and thrombosis risk.

W Zhu, J A Buffa, Z Wang, M Warrier, R Schugar, D M Shih, N Gupta, J C Gregory, E Org, X Fu and 5 more

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

Article in Journal of thrombosis and haemostasis : JTH, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 2% 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

93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.

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33 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

15 authors at 3 institutions in 1 country.

W ZhuLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J A BuffaLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Z WangLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
M WarrierLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
R SchugarLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
D M ShihLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
N GuptaLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J C GregoryLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
E OrgDepartments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
X FuDepartments of Human Genetics and Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
L LiLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J A DiDonatoLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
A J LusisLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
J M BrownLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
S L HazenLerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Cleveland Clinic Lerner College of Medicine · USUniversity 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
Diet, Gut Microbiota, and Heart FailureR01HL126827 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L, TANG, WAI HONG WILSON · 2016 to 2019
$3.1M
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
Enzymatic Control of Trimethylamineoxide (TMAO)Induced AtherosclerosisR01HL122283 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK · 2014 to 2018
$2.0M
Microbial Trimethylamine Lyases and AtherosclerosisR01HL130819 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WANG, ZENENG · 2016 to 2019
$1.7M
Molecular Medicine Training ProgramT32GM088088 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI SMITH, JONATHAN D · 2011 to 2020
$1.7M
NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL122283NHLBI NIH HHS R01 HL126827NHLBI NIH HHS R01 HL130819NIDDK NIH HHS R01 DK106000NIGMS NIH HHS T32 GM088088
6 · The paper itself

Abstract

Essentials Microbe-dependent production of trimethylamine N-oxide (TMAO) contributes to thrombosis risk. The impact of host flavin monooxygenase 3 (FMO3) modulation on platelet function is unknown. Genetic manipulation of FMO3 in mice alters systemic TMAO levels and thrombosis potential. Genetic manipulation of FMO3 is associated with alteration of gut microbial community structure. SUMMARY: Background Gut microbes play a critical role in the production of trimethylamine N-oxide (TMAO), an atherogenic metabolite that impacts platelet responsiveness and thrombosis potential. Involving both microbe and host enzymatic machinery, TMAO generation utilizes a metaorganismal pathway, beginning with ingestion of trimethylamine (TMA)-containing dietary nutrients such as choline, phosphatidylcholine and carnitine, which are abundant in a Western diet. Gut microbial TMA lyases use these nutrients as substrates to produce TMA, which upon delivery to the liver via the portal circulation, is converted into TMAO by host hepatic flavin monooxygenases (FMOs). Gut microbial production of TMA is rate limiting in the metaorganismal TMAO pathway because hepatic FMO activity is typically in excess. Objectives FMO3 is the major FMO responsible for host generation of TMAO; however, a role for FMO3 in altering platelet responsiveness and thrombosis potential in vivo has not yet been explored. Methods The impact of FMO3 suppression (antisense oligonucleotide-targeting) and overexpression (as transgene) on plasma TMAO levels, platelet responsiveness and thrombosis potential was examined using a murine FeCl

Indexed as

AnimalsBlood PlateletsCarotid Artery, CommonCarotid Artery ThrombosisChloridesFerric CompoundsGastrointestinal MicrobiomeGene Knockdown TechniquesHumansLiverMethylaminesMiceMice, Inbred C57BLOligonucleotides, AntisenseOxygenasesPlatelet-Rich PlasmaChloridesdimethylaniline monooxygenase (N-oxide forming)ferric chlorideFerric CompoundsMethylaminesOligonucleotides, AntisenseOxygenasestrimethyloxamineblood plateletscardiovascular diseasecholinegut microbethrombosis

Identifiers

PMID29981269
PMCPMC6156942
OpenAlexW2829671626

What OpenQuestion holds

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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.