Evidence map›Paper›PMID 23334216›Full record

ArticleCardiovascular research2013

Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts.

Luis Villacorta, Lin Chang, Sonia R Salvatore, Tomonaga Ichikawa, Jifeng Zhang, Danica Petrovic-Djergovic, Lingyun Jia, Harald Carlsen, Francisco J Schopfer, Bruce A Freeman and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

75 citing papers in PubMed, 113 citations in OpenAlex.

  1. Trial
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  11. Nitro-oleic acid regulates T cell activation through post-translational modification of calcineurin.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Nitro Fatty Acids (NOMolecules (Basel, Switzerland) · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

15 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

11 authors at 4 institutions in 4 countries.

Luis VillacortaCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, North Campus Research Complex Building 26 Room 355S, 2800 Plymouth Road, Ann Arbor, MI, USA. luisvill@umich.edu
Lin Chang
Sonia R Salvatore
Tomonaga Ichikawa
Jifeng Zhang
Danica Petrovic-Djergovic
Lingyun Jia
Harald Carlsen
Francisco J Schopfer
Bruce A Freeman
Y Eugene Chen
University of Michigan–Ann Arbor · USUniversity of Pittsburgh · USUniversity of Miyazaki · JPUniversity of Oslo · NO

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T · 2011 to 2020
$26.1M
The Role of PPAR-gamma in Vascular Lesion FormationR01HL068878 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2002 to 2019
$7.6M
Redox-Derived Pulmonary Anti-Inflammatory MediatorsR01HL064937 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2000 to 2015
$5.6M
NITRIC OXIDE REGULATION OF VASCULAR OXIDANT INJURYR01HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 1998 to 2007
$3.3M
Anti-Inflammatory Lipid Mediators in AsthmaR01HL132550 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN, HOLGUIN, FERNANDO · 2016 to 2019
$2.9M
Nitro-Fatty Acids and Nrf2 in Vascular RemodelingR01HL105114 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2010 to 2014
$2.6M
Nitroalkenes and Blood Pressure RegulationR01HL089544 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2008 to 2012
$2.0M
Formation of Omega 3-Derived Electrophiles During InflammationR01AT006822 · NCCIH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHOPFER, FRANCISCO JOSE · 2011 to 2015
$1.8M
Nitroalkene-Mediated Vascular Protection and Ischemic StrokeR01NS066652 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE · 2011 to 2014
$1.3M
NCCIH NIH HHS R01-AT006822-01NHLBI NIH HHS P01-HL103455NHLBI NIH HHS R01-HL058115NHLBI NIH HHS R01 HL064937NHLBI NIH HHS R01-HL064937NHLBI NIH HHS R01 HL068878NHLBI NIH HHS R01 HL105114NHLBI NIH HHS R01-HL105114NHLBI NIH HHS R01 HL132550NHLBI NIH HHS R01-HL68878NHLBI NIH HHS R01-HL89544NINDS NIH HHS R01 NS066652
6 · The paper itself

Abstract

aimsElectrophilic fatty acid nitroalkene derivatives, products of unsaturated fatty acid nitration, exert long-term cardiovascular protection in experimental models of metabolic and cardiovascular diseases. The goal of this study is to examine the effects of nitro-fatty acids in the regulation of upstream signalling events in nuclear factor-κB (NF-κB) activation and determine whether low-dose acute administration of nitro-fatty acids reduces vascular inflammation in vivo. METHODS AND

resultsUsing NF-κB-luciferase transgenic mice, it was determined that pre-emptive treatment with nitro-oleic acid (OA-NO2), but not oleic acid (OA) inhibits lipopolysaccharide (LPS)-induced NF-κB activation both in vivo and in isolated macrophages. Acute intravenous administration of OA-NO2 was equally effective to inhibit leukocyte recruitment to the vascular endothelium assessed by intravital microscopy and significantly reduces aortic expression of adhesion molecules. An acute treatment with OA-NO2 in vivo yielding nanomolar concentrations in plasma, is sufficient to inhibit LPS-induced Toll-like receptor 4 (TLR4)-induced cell surface expression in leukocytes and NF-κB activation. In vitro experiments reveal that OA-NO2 suppresses LPS-induced TLR4 signalling, inhibitor of κB (IκBα) phosphorylation and ubiquitination, phosphorylation of the IκB kinase (IKK), impairing the recruitment of the TLR4 and TNF receptor associated factor 6 (TRAF6) to the lipid rafts compartments.

conclusionThese studies demonstrate that acute administration of nitro-fatty acids is effective to reduce vascular inflammation in vivo. These findings reveal a direct role of nitro-fatty acids in the disruption of the TLR4 signalling complex in lipid rafts, upstream events of the NF-κB pathway, leading to resolution of pro-inflammatory activation of NF-κB in the vasculature.

Indexed as

AnimalsCell AdhesionCells, CulturedHumansLipopolysaccharidesMembrane MicrodomainsMiceMice, Inbred C57BLNF-kappa BNitric OxideOleic AcidsPhosphorylationSignal TransductionToll-Like Receptor 4VasculitisLipopolysaccharidesNF-kappa BNitric OxideOleic AcidsTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID23334216
PMCPMC3598418
OpenAlexW2161481261

What OpenQuestion holds

Textmetadata
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.