Evidence map›Paper›PMID 25814626›Full record

ArticleJournal of the American Heart Association2015

A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.

R A van Dijk, A J F Duinisveld, A F Schaapherder, A Mulder-Stapel, J F Hamming, J Kuiper, O J de Boer, A C van der Wal, F D Kolodgie, R Virmani and 1 more

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

Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 3 pooled it
3.9field-weighted citation impact, top 6% 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

60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020
    Pooled it
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  5. CD80Cell communication and signaling : CCS · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

R A van DijkDepartment of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (D., D., M.S., H., L.).
A J F DuinisveldDepartment of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (D., D., M.S., H., L.).
A F SchaapherderDepartment of Transplantation Surgery, Leiden University Medical Center, Leiden, The Netherlands (S.).
A Mulder-StapelDepartment of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (D., D., M.S., H., L.).
J F HammingDepartment of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (D., D., M.S., H., L.).
J KuiperGorlaeus Laboratories, Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands (K.).
O J de BoerDepartment of Pathology, Academic Medical Center, Amsterdam, The Netherlands (B., W.).
A C van der WalDepartment of Pathology, Academic Medical Center, Amsterdam, The Netherlands (B., W.).
F D KolodgieCVPath Institute Inc., Gaithersburg, MD (K., V.).
R VirmaniCVPath Institute Inc., Gaithersburg, MD (K., V.).
J H N LindemanDepartment of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands (D., D., M.S., H., L.).
Leiden University Medical Center · NLAcademic Medical Center · NLCVPath Institute · USCentre for Human Drug Research · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExperimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease. METHODS AND

resultsA systematic analysis was performed on 114 well-characterized perirenal aortic specimens with immunostaining for T-cell subsets (CD3/4/8/45RA/45RO/FoxP3) and the Th1/non-Th1/Th17 ratio (CD4(+)T-bet(+)/CD4(+)T-bet(-)/CD4(+)/interleukin-17(+) double staining). CD20 and CD138 were used to identify B cells and plasma cells, while B-cell maturation was evaluated by AID/CD21 staining and expression of lymphoid homeostatic CXCL13. Scattered CD4 and CD8 cells with a T memory subtype were found in normal aorta and early, nonprogressive lesions. The total number of T cells increases in progressive atherosclerotic lesions (≈1:5 CD4/CD8 T-cell ratio). A further increase in medial and adventitial T cells is found upon progression to vulnerable lesions.This critical stage is further hallmarked by de novo formation of adventitial lymphoidlike structures containing B cells and plasma cells, a process accompanied by transient expression of CXCL13. A dramatic reduction of T-cell subsets, disappearance of lymphoid structures, and loss of CXCL13 expression characterize postruptured lesions. FoxP3 and Th17 T cells were minimally present throughout the atherosclerotic process.

conclusionsTransient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture, indicates a "critical" change in the inflammatory footprint before and during plaque destabilization.

Indexed as

Adaptive ImmunityAdultAortaAtherosclerosisB-LymphocytesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesChemokine CXCL13Disease ProgressionFemaleHumansMaleMiddle AgedPlaque, AtheroscleroticPlasma CellsT-Lymphocyte SubsetsChemokine CXCL13adaptive immunityaortaatherosclerosisinflammationnecrotic coreneovesselvulnerable plaque

Identifiers

PMID25814626
PMCPMC4579929
OpenAlexW2110947961

What OpenQuestion holds

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LicenceCC BY-NC
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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.