Evidence map›Paper›PMID 24833794›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

α5β1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis.

Arif Yurdagul, Jonette Green, Patrick Albert, Marshall C McInnis, Andrew P Mazar, A Wayne Orr

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
4.6field-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

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Article
  5. Review
  6. Review
  7. Anti-Atherogenic Mechanisms and Therapies.Current atherosclerosis reports · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Vascular Extracellular Matrix in Atherosclerosis.International journal of molecular sciences · 2024
    Review
  17. Article
  18. Review
  19. Article
  20. Article

16 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

6 authors at 1 institution in 1 country.

Arif YurdagulFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.).
Jonette GreenFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.).
Patrick AlbertFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.).
Marshall C McInnisFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.).
Andrew P MazarFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.).
A Wayne OrrFrom the Departments of Pathology (A.Y., J.G., P.A., M.C.M., A.W.O.) and Cell Biology and Anatomy (A.Y., A.W.O.), Louisiana State University Health Sciences Center, Shreveport; and Chemistry of Life Processes Institute, Northwestern University, Evanston, IL (A.P.M.). aorr@lsuhsc.edu.
Northwestern University · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Matrix Signaling in Endothelial Cell DysfunctionR01HL098435 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ORR, ANTHONY WAYNE · 2010 to 2020
$3.2M
NCI NIH HHS P30 CA060553NHLBI NIH HHS R01 HL098435NHLBI NIH HHS R01HL098435
6 · The paper itself

Abstract

objectiveEndothelial cell activation drives early atherosclerotic plaque formation. Both fibronectin deposition and accumulation of oxidized low-density lipoprotein (oxLDL) occur early during atherogenesis, and both are implicated in enhanced endothelial cell activation. However, interplay between these responses has not been established. The objective of our study was to determine whether endothelial matrix composition modulates the inflammatory properties of oxLDL. APPROACH AND

resultsWe now show that oxLDL-induced nuclear factor-κB activation, proinflammatory gene expression, and monocyte binding are significantly enhanced when endothelial cells are attached to fibronectin compared with basement membrane proteins. This enhanced response does not result from altered oxLDL receptor expression, oxLDL uptake, or reactive oxygen species production, but results from oxLDL-induced activation of the fibronectin-binding integrin α5β1. Preventing α5β1 signaling (blocking antibodies, knockout cells) inhibits oxLDL-induced nuclear factor-κB activation and vascular cell adhesion molecule-1 expression. Furthermore, oxLDL drives α5β1-dependent integrin signaling through the focal adhesion kinase pathway, and focal adhesion kinase inhibition (PF-573228, small interfering RNA) blunts oxLDL-induced nuclear factor-κB activation, vascular cell adhesion molecule-1 expression, and monocyte adhesion. Last, treatment with the α5β1 signaling inhibitor, ATN-161, significantly blunts atherosclerotic plaque development in apolipoprotein E-deficient mice, characterized by reduced vascular cell adhesion molecule-1 expression and macrophage accumulation without affecting fibrous cap size.

conclusionsOur data suggest that α5β1-mediated cross-talk between fibronectin and oxLDL regulates inflammation in early atherogenesis and that therapeutics that inhibit α5 integrins may reduce inflammation without adversely affecting plaque structure.

Indexed as

Signal TransductionAnimalsAnti-Inflammatory AgentsApolipoproteins EAtherosclerosisCell AdhesionCells, CulturedCoculture TechniquesDisease Models, AnimalEndothelial CellsExtracellular MatrixFibronectinsFibrosisHumansInflammationInflammation MediatorsAnti-Inflammatory AgentsApolipoproteins EFibronectinsInflammation MediatorsIntegrin alpha5beta1Lipoproteins, LDLNF-kappa Boxidized low density lipoproteinVascular Cell Adhesion Molecule-1atherosclerosisfibronectinsinflammationintegrin alpha5beta1lipoproteins, LDL

Identifiers

PMID24833794
PMCPMC4096780
OpenAlexW2096108882

What OpenQuestion holds

Textmetadata
LicenceTDM
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.