Evidence map›Paper›PMID 29274344›Full record

ArticleJournal of molecular and cellular cardiology2018

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release.

Yana Dautova, Alexander N Kapustin, Kevin Pappert, Matthias Epple, Hanneke Okkenhaug, Simon J Cook, Catherine M Shanahan, Martin D Bootman, Diane Proudfoot

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.6field-weighted citation impact, top 16% 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, 42 citations in OpenAlex.

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  13. Emerging role of exosomes in vascular diseases.Frontiers in cardiovascular medicine · 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

9 authors at 4 institutions in 2 countries.

Yana DautovaSignalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
Alexander N KapustinCardiovascular Division, James Black Centre, King's College London,125 Coldharbour Lane, London SE5 9NU, UK.
Kevin PappertInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Essen-Duisburg, Essen 45117, Germany.
Matthias EppleInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Essen-Duisburg, Essen 45117, Germany.
Hanneke OkkenhaugSignalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
Simon J CookSignalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK.
Catherine M ShanahanCardiovascular Division, James Black Centre, King's College London,125 Coldharbour Lane, London SE5 9NU, UK.
Martin D BootmanSchool of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK.
Diane ProudfootSignalling Programme, Babraham Institute, Babraham, Cambridge CB22 3AT, UK. Electronic address: diane.proudfoot@babraham.ac.uk.
Babraham Institute · GBKing's College London · GBUniversity of Duisburg-Essen · DEThe Open University · GB

Funding

Biotechnology and Biological Sciences Research Council BBS/E/B/000C0417British Heart Foundation FS/11/21/28691British Heart Foundation PG/17/37/33023British Heart Foundation RG/17/2/32808
6 · The paper itself

Abstract

aimsCalcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. METHODS AND

resultsUsing ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release.

conclusionsCaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and pro-calcific potential of microcalcification.

Indexed as

AdultCalcium PhosphatesCaspase 1Cells, CulturedEnzyme ActivationExosomesFemaleHumansInflammasomesInterleukin-1betaMaleMiddle AgedMuscle, Smooth, VascularMyocytes, Smooth MusclePhosphorylationSyk Kinasecalcium phosphateCalcium PhosphatesCaspase 1InflammasomesInterleukin-1betaSyk KinaseCalcium phosphate particlesCaspase-1CytokinesExosomesSYKVascular smooth muscle

Identifiers

PMID29274344
PMCPMC5823844
OpenAlexW2777560001

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.