Evidence map›Paper›PMID 40287595›Full record

ArticleCellular and molecular life sciences : CMLS2025

Calciprotein particle-activated endothelial cells aggravate smooth muscle cell calcification via paracrine signalling.

Lian Feenstra, Lara W Zeper, Brenda van de Langenberg, Eveline J E M Kahlman, Guido de La Roij, Melanie Reijrink, Benoit Bernay, Laurent Chatre, Jeroen Kuipers, Ben N G Giepmans and 11 more

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In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

21 authors.

Lian FeenstraDepartment of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Lara W ZeperDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Brenda van de LangenbergDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Eveline J E M KahlmanDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Guido de La RoijDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Melanie ReijrinkDepartment of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Benoit BernayNormandie Univ, UNICAEN, US EMerode, Plateform Proteogen, 14000, Caen, France.
Laurent ChatreUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, 14000, Caen, France.
Jeroen KuipersDepartment of Biomedical Sciences, University Medical Center of Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Ben N G GiepmansDepartment of Biomedical Sciences, University Medical Center of Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Mirjam F MastikDepartment of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Wierd KooistraDepartment of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Monique E LodewijkDepartment of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Malou ZuidscherwoudeDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Robert A PolDepartment of Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
TransplantLines Investigators
Edward R SmithDepartment of Nephrology, Royal Melbourne Hospital, Parkville, VIC, Australia.
Guido KrenningDepartment of Clinical Pharmacy and Pharmacology, University Medical Center of Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jeroen H F de BaaijDepartment of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.
Jan-Luuk Hillebrands *Department of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. j.l.hillebrands@umcg.nl.ORCID http://orcid.org/0000-0003-3135-3274
Joost G J Hoenderop *Department of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands. joost.hoenderop@radboudumc.nl.ORCID http://orcid.org/0000-0002-1816-8544

Funding

Health~Holland LSHM17034-SGFNederlandse Organisatie voor Wetenschappelijk Onderzoek 184.034.014Nierstichting 16TKI02Nierstichting 21OK022ZonMw 91111.006
6 · The paper itself

Abstract

backgroundVascular calcification is highly prevalent in Chronic Kidney Disease (CKD) and is associated with markedly increased cardiovascular risk. High serum phosphate in CKD increases calcification propensity via generation of circulating calciprotein particles (CPP2), crystalline nanoaggregates composed of calcium, phosphate, and serum proteins. CPP2 induce vascular calcification in vascular smooth muscle cells (VSMCs) in vitro. In vivo, endothelial cells, rather than VSMCs are primarily exposed to CPP2, yet understanding the influence of endothelial cells on vascular calcification is limited.

methodsWe investigated calcification-promoting signalling by endothelial cells on VSMCs. Effects of CPP2 exposure to endothelial cells on CPP2 uptake, endothelial cell activation, and endothelial cell-derived secretome were studied. Effects of the secretome on VSMC calcification were investigated. Using NanoString nCounter analysis the effects of CPP2-activated endothelial cell-conditioned medium on VSMCs gene expression were mapped.

resultsEndothelial cells internalise CPP2 and elevate ICAM-1, E-selectin, and VCAM-1-mRNA expression, indicating endothelial activation. VSMCs cultured in conditioned medium from CPP2-activated endothelial cells demonstrated enhanced calcification, suggesting that CPP2-activated endothelial cells release pro-calcifying soluble factors. Mass spectrometry was utilized to identify 1171 proteins in the CPP2-activated endothelial cells' secretome. Among these, 76 proteins were differentially expressed compared to control endothelial cells' secretome, including proteins related to blood vessel development, extracellular matrix remodelling, and oxidative stress-related processes. Finally, endothelial cell-derived paracrine factors present in conditioned medium enhanced mRNA-expression of calcification-related factors in VSMCs.

conclusionsCPP2-activated endothelial cells promote VSMC calcification via paracrine signalling. In response to these paracrine factors, VSMCs increase the expression of pro-calcification genes.

Indexed as

Endothelial CellsMyocytes, Smooth MuscleParacrine CommunicationVascular CalcificationAnimalsCells, CulturedCulture Media, ConditionedE-SelectinHumansIntercellular Adhesion Molecule-1Muscle, Smooth, VascularRenal Insufficiency, ChronicVascular Cell Adhesion Molecule-1Culture Media, ConditionedE-SelectinIntercellular Adhesion Molecule-1Vascular Cell Adhesion Molecule-1Calciprotein particlesChronic kidney diseaseEndothelial cell activationParacrine signallingVascular calcification

Identifiers

PMID40287595
PMCPMC12033162

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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.