Evidence map›Paper›PMID 34440866›Full record

ArticleCells2021

Development of the BioHybrid Assay: Combining Primary Human Vascular Smooth Muscle Cells and Blood to Measure Vascular Calcification Propensity.

Armand M G Jaminon, Asim C Akbulut, Niko Rapp, Rafael Kramann, Erik A L Biessen, Lieve Temmerman, Barend Mees, Vincent Brandenburg, Robert Dzhanaev, Willi Jahnen-Dechent and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Hypotaurine Reduces Glucose-Mediated Vascular Calcification.Acta physiologica (Oxford, England) · 2025
    Article
  2. Why Current Detection of Vascular Calcification Falls Short and How to Improve on It.TH open : companion journal to thrombosis and haemostasis · 2024
    Review
  3. Review
  4. Article
  5. Article
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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

14 authors at 5 institutions in 3 countries.

Armand M G JaminonDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-1844-2363
Asim C AkbulutDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
Niko RappDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
Rafael KramannInstitute of Experimental Medicine and Systems Biology, RWTH Aachen University, 52074 Aachen, Germany.
Erik A L BiessenDepartment of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 HX Maastricht, The Netherlands.
Lieve TemmermanDepartment of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, 6229 HX Maastricht, The Netherlands.
Barend MeesDepartment of Vascular Surgery, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
Vincent BrandenburgDepartment of Cardiology, Rhein-Maas-Klinikum Würselen, 52146 Würselen, Germany.ORCID 0000-0001-5959-3523
Robert DzhanaevHelmholtz Institute for Biomedical Engineering, Biointerface Group, RWTH Aachen University, 52074 Aachen, Germany.
Willi Jahnen-DechentHelmholtz Institute for Biomedical Engineering, Biointerface Group, RWTH Aachen University, 52074 Aachen, Germany.ORCID 0000-0003-1315-4407
Juergen FloegeDepartment of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, 52074 Aachen, Germany.
Jouni UittoDepartment of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Chris P ReutelingspergerDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.ORCID 0000-0002-2334-9403
Leon J SchurgersDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.ORCID 0000-0001-7867-6957
Maastricht University Medical Centre · NLRWTH Aachen University · DEMaastricht University · NLKlinikum Rheine · DEThomas Jefferson University · US

Funding

European Union's Horizon 2020 research and innovation programmes 722609 and 764474NWO ZonMw MKMD 40-42600-98-13007the Deutsche Forschungsgemeinschaft TRR 219 - Project-ID 322900939
6 · The paper itself

Abstract

backgroundVascular calcification is an active process that increases cardiovascular disease (CVD) risk. There is still no consensus on an appropriate biomarker for vascular calcification. We reasoned that the biomarker for vascular calcification is the collection of all blood components that can be sensed and integrated into a calcification response by human vascular smooth muscle cells (hVSMCs).

methodsWe developed a new cell-based high-content assay, the BioHybrid assay, to measure in vitro calcification. The BioHybrid assay was compared with the o-Cresolphthalein assay and the T50 assay. Serum and plasma were derived from different cohort studies including chronic kidney disease (CKD) stages III, IV, V and VD (on dialysis), pseudoxanthoma elasticum (PXE) and other cardiovascular diseases including serum from participants with mild and extensive coronary artery calcification (CAC). hVSMCs were exposed to serum and plasma samples, and in vitro calcification was measured using AlexaFluor

resultsThe BioHybrid assay measured the kinetics of calcification in contrast to the endpoint o-Cresolphthalein assay. The BioHybrid assay was more sensitive to pick up differences in calcification propensity than the T50 assay as determined by measuring control as well as pre- and post-dialysis serum samples of CKD patients. The BioHybrid response increased with CKD severity. Further, the BioHybrid assay discriminated between calcification propensity of individuals with a high CAC index and individuals with a low CAC index. Patients with PXE had an increased calcification response in the BioHybrid assay as compared to both spouse and control plasma samples. Finally, vitamin K1 supplementation showed lower in vitro calcification, reflecting changes in delta Agatston scores. Lower progression within the BioHybrid and on Agatston scores was accompanied by lower dephosphorylated-uncarboxylated matrix Gla protein levels.

conclusionThe BioHybrid assay is a novel approach to determine the vascular calcification propensity of an individual and thus may add to personalised risk assessment for CVD.

Indexed as

alpha-2-HS-GlycoproteinBiomarkersCalcium-Binding ProteinsCardiovascular DiseasesCells, CulturedExtracellular Matrix ProteinsFluorescent DyesHematologic TestsHumansKineticsMatrix Gla ProteinMuscle, Smooth, VascularRenal DialysisRenal Insufficiency, ChronicVascular CalcificationVitamin K 1alpha-2-HS-GlycoproteinBiomarkersCalcium-Binding ProteinsExtracellular Matrix ProteinsFluorescent DyesMatrix Gla ProteinVitamin K 1BioHybridcardiovascular diseasefetuin-Amatrix Gla proteinvascular calcificationvascular smooth muscle cellsvitamin Kvitamin K antagonist

Identifiers

PMID34440866
PMCPMC8391733
OpenAlexW3195705740

What OpenQuestion holds

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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.