Evidence map›Paper›PMID 27283739›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Neutrophil Proteases Promote Experimental Abdominal Aortic Aneurysm via Extracellular Trap Release and Plasmacytoid Dendritic Cell Activation.

Huimin Yan, Hui-Fang Zhou, Antonina Akk, Ying Hu, Luke E Springer, Terri L Ennis, Christine T N Pham

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.

  1. Pooled it
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  4. The role of neutrophils in the pathogenesis of abdominal aortic aneurysms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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21 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

7 authors at 1 institution in 1 country.

Huimin Yan *John Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Hui-Fang Zhou *John Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Antonina Akk *John Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Ying HuJohn Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Luke E SpringerJohn Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Terri L EnnisJohn Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Christine T N PhamJohn Cochran VA Medical Center, Saint Louis, Missouri USA; the Department of Medicine, Division of Rheumatology and the Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
John Cochran VA Medical Center · US

Funding

METHODS IN MOLECULAR IMAGING AND TARGETED THERAPEUTICSR01HL073646 · NHLBI · WASHINGTON UNIVERSITY · PI WICKLINE, SAMUEL A · 2004 to 2016
$13.7M
Viral Discovery in Rheumatoid ArthritisP30AR048335 · NIAMS · WASHINGTON UNIVERSITY · PI BYUN, MINJI · 2001 to 2015
$8.9M
COMPLEMENT CONVERTASE: ASSEMBLY, FUNCTION AND REGULATIONR01AI051436 · NIAID · WASHINGTON UNIVERSITY · PI HOURCADE, DENNIS EMIL · 2003 to 2016
$3.7M
Inhibition of NF-kB with siRNA/Peptide Nanoparticles for Arthritis TreatmentR01AR067491 · NIAMS · WASHINGTON UNIVERSITY · PI PHAM, CHRISTINE T., WICKLINE, SAMUEL A · 2015 to 2019
$1.8M
Immune-mediated pathways in pathogenesis of abdominal aortic aneurysmI01BX002714 · VA · ST. LOUIS VA MEDICAL CENTER · PI PHAM, CHRISTINE T. · 2015 to 2020
–
BLRD VA I01 BX002714NHLBI NIH HHS R01 HL073646NIAID NIH HHS R01 AI051436NIAMS NIH HHS P30 AR048335NIAMS NIH HHS R01 AR067491
6 · The paper itself

Abstract

objectiveWe previously established that neutrophil-derived dipeptidyl peptidase I (DPPI) is essential for experimental abdominal aortic aneurysm (AAA) development. Because DPPI activates several neutrophil serine proteases, it remains to be determined whether the AAA-promoting effect of DPPI is mediated by neutrophil serine proteases. APPROACH AND

resultsUsing an elastase-induced AAA model, we demonstrate that the absence of 2 neutrophil serine proteases, neutrophil elastase and proteinase-3, recapitulates the AAA-resistant phenotype of DPPI-deficient mice. DPPI and neutrophil serine proteases direct the in vitro and in vivo release of extracellular structures termed neutrophil extracellular traps (NETs). Administration of DNase1, which dismantles NETs, suppresses elastase-induced AAA in wild-type animals and in DPPI-deficient mice reconstituted with wild-type neutrophils. NETs also contain the cathelicidin-related antimicrobial peptide that complexes with self-DNA in recruiting plasmacytoid dendritic cells (pDCs), inducing type I interferons (IFNs) and promoting AAA in DPPI-deficient mice. Conversely, depletion of pDCs or blockade of type I IFNs suppresses experimental AAA. Moreover, we find an abundance of human cathelicidin peptide, a 37 amino acid sequence starting with 2 leucines and the human orthologue of cathelicidin-related antimicrobial peptide, in the vicinity of pDCs in human AAA tissues. Increased type I IFN mRNA expression is observed in human AAA tissues and circulating IFN-α is detected in ≈50% of the AAA sera examined.

conclusionsThese results suggest that neutrophil protease-mediated NET release contributes to elastase-induced AAA through pDC activation and type I IFN production. These findings increase our understanding of the pathways underlying AAA inflammatory responses and suggest that limiting NET, pDC, and type I IFN activities may suppress aneurysm progression.

Indexed as

AnimalsAorta, AbdominalAortic Aneurysm, AbdominalCathepsin CCells, CulturedDendritic CellsDisease Models, AnimalExtracellular TrapsGenotypeHumansInterferon Type ILeukocyte ElastaseMice, Inbred C57BLMice, KnockoutMyeloblastinNeutrophilsCathepsin CCtsc protein, mouseInterferon Type ILeukocyte ElastaseMyeloblastinaortic aneurysm, abdominaldendritic cellsextracellular trapsinterferon type Ineutrophil extracellular trapsplasmacytoid dendritic cells

Identifiers

PMID27283739
PMCPMC4965335
OpenAlexW2411586275

What OpenQuestion holds

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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.