Evidence map›Paper›PMID 30304051›Full record

ArticlePloS one2018

Molecular imaging of MMP activity discriminates unstable from stable plaque phenotypes in shear-stress induced murine atherosclerosis.

Robert Seifert, Michael T Kuhlmann, Sarah Eligehausen, Friedemann Kiefer, Sven Hermann, Michael Schäfers

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

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 28% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

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  13. Detection of Early Endothelial Dysfunction by Optoacoustic Tomography.International journal of molecular sciences · 2023
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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.

Robert SeifertEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.ORCID 0000-0001-5985-7701
Michael T KuhlmannEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
Sarah EligehausenEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
Friedemann KieferEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
Sven HermannEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
Michael SchäfersEuropean Institute for Molecular Imaging (EIMI), University of Münster, Münster, Germany.
University of Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAs atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in plaque progression and destabilisation and are therefore promising targets to characterize rupture-prone unstable plaques. This study aims at evaluating MMP imaging to discriminate unstable from stable plaque phenotypes.

methodsApoE deficient mice (ApoE-/-) on a high cholesterol diet underwent implantation of a tapered cuff around the right common carotid artery (CCA) inducing a highly inflamed atherosclerotic plaque upstream (US) and a more stable plaque phenotype downstream (DS) of the cuff. 8 weeks after surgery, the MMP inhibitor-based photoprobe Cy5.5-AF443 was administered i.v. 3h prior to in situ and ex vivo fluorescence reflectance imaging of the CCAs. Thereafter, CCAs were analysed regarding plaque size, presence of macrophages, and MMP-2 and MMP-9 concentrations by immunohistochemistry and ELISA.

resultsWe found a significantly higher uptake of Cy5.5-AF443 in US as compared to DS plaques in situ (1.29 vs. 1.06 plaque-to-background ratio; p<0.001), which was confirmed by ex vivo measurements. Immunohistochemistry revealed a higher presence of macrophages, MMP-2 and MMP-9 in US compared to DS plaques. Accordingly, MMP-2 concentrations were significantly higher in US plaques (47.2±7.6 vs. 29.6±4.6 ng/mg; p<0.05).

conclusionsIn the ApoE-/- cuff model MMP-2 and MMP-9 activities are significantly higher in upstream low shear stress-induced unstable atherosclerotic plaques as compared to downstream more stable plaque phenotypes. MMP inhibitor-based fluorescence molecular imaging allows visualization of these differences in shear stress-induced atherosclerosis.

Indexed as

AnimalsApolipoproteins ECarbocyaninesDisease Models, AnimalDisease ProgressionHumansMacrophagesMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMiceMolecular ImagingPlaque, AtheroscleroticShear StrengthStress, PhysiologicalApolipoproteins ECarbocyaninesCY5.5 cyanine dyeMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMmp2 protein, mouseMmp9 protein, mouse

Identifiers

PMID30304051
PMCPMC6179381
OpenAlexW2897524210

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.