Evidence map›Paper›PMID 21220319›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Unexpected protective role for Toll-like receptor 3 in the arterial wall.

Jennifer E Cole, Tina J Navin, Amanda J Cross, Michael E Goddard, Lena Alexopoulou, Anuja T Mitra, Alun H Davies, Richard A Flavell, Marc Feldmann, Claudia Monaco

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
7.5field-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

84 citing papers in PubMed, 167 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. The Role of TLRs in Obesity and Its Related Metabolic Disorders.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Review
  7. TRIF-dependent signaling and its role in liver diseases.Frontiers in cell and developmental biology · 2024
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. MyD88: At the heart of inflammatory signaling and cardiovascular disease.Journal of molecular and cellular cardiology · 2021
    Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 3 countries.

Jennifer E ColeKennedy Institute of Rheumatology, Faculty of Medicine, Imperial College, London W6 8LH, United Kingdom.
Tina J Navin
Amanda J Cross
Michael E Goddard
Lena Alexopoulou
Anuja T Mitra
Alun H Davies
Richard A Flavell
Marc Feldmann
Claudia Monaco
Imperial College London · GBYale University · US

Funding

Arthritis Research UKBritish Heart Foundation PG/11/46/28979
6 · The paper itself

Abstract

The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE(-/-) mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall.

Indexed as

Signal TransductionAnimalsCarotid ArteriesCarotid Artery DiseasesFemaleHumansHypercholesterolemiaInterferon InducersMaleMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MusclePoly I-CToll-Like Receptor 3Interferon InducersPoly I-CTLR3 protein, humanTLR3 protein, mouseToll-Like Receptor 3

Identifiers

PMID21220319
PMCPMC3038746
OpenAlexW1983838712

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.