Evidence map›Paper›PMID 27716072›Full record

ArticleBMC cardiovascular disorders2016

Wnt signaling contributes to vascular calcification by induction of matrix metalloproteinases.

Christian Freise, Nadja Kretzschmar, Uwe Querfeld

Open access · goldAbstract read
In one paragraph

Article in BMC cardiovascular disorders, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. FHL2 in arterial medial calcification in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Article
  5. Similarities and Differences of Vascular Calcification in Diabetes and Chronic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024
    Review
  6. Review
  7. Review
  8. Sclerostin Protects Against Vascular Calcification Development in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Effects of Eicosapentaenoic Acid on Arterial Calcification.International journal of molecular sciences · 2020
    Review
  18. The Role of Sclerostin in Bone and Ectopic Calcification.International journal of molecular sciences · 2020
    Review
  19. Article
  20. 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

3 authors at 1 institution in 1 country.

Christian FreiseCenter for Cardiovascular Research, Charité - University Medicine, Campus Mitte, Hessische Str. 3-4, 10115, Berlin, Germany. christian.freise@charite.de.ORCID 0000-0003-2602-226X
Nadja KretzschmarCenter for Cardiovascular Research, Charité - University Medicine, Campus Mitte, Hessische Str. 3-4, 10115, Berlin, Germany.
Uwe QuerfeldCenter for Cardiovascular Research, Charité - University Medicine, Campus Mitte, Hessische Str. 3-4, 10115, Berlin, Germany.
Charité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVascular calcifications such as arteriosclerosis, which is characterized by a calcificiation of the tunica media, represent major comorbidities e.g. in patients with chronic kidney disease (CKD). An essential step during the development of arteriosclerosis is the transdifferentiation/calcification of vascular smooth muscle cells (VSMC) resembling osteogenesis. The matrix metalloproteinases (MMP)-2 and -9 were shown to promote these VSMC calcifications and their inhibition is of therapeutic value to prevent arteriosclerosis in preclinical studies. Aiming for an understanding of the underlying regulatory mechanisms of MMPs we here investigated, if the MMP-mediated VSMC calcification involves altered signaling of the Wnt pathway, which is known to impact osteogenesis.

methodsWe used an experimental in vitro model of vascular calcification. Transdifferentiation/calcification of murine VSMC was induced by elevated calcium and phosphorus levels. Calcification was assessed by calcium and alkaline phosphatase measurements. Activation/activity of the gelatinases MMP-2 and MMP-9 was assessed by conversion of fluorescence-labelled substrates. Activation of the Wnt pathway was analysed by a reporter gene assay.

resultsBesides pro-calcifying culture conditions, also activation of Wnt signaling by a specific agonist (under normal culture conditions) stimulated VSMC-calcification accompanied by enhanced expression and secretion of the gelatinases MMP-2 and -9. Vice versa, recombinant MMP-2 and -9 induced a time-delayed activation of Wnt signaling after 72 h in VSMC but showed no direct effects after 24-48 h. These effects were blocked by pharmacological inhibition of MMPs or of Wnt signaling.

conclusionsOur study suggests that the pro-calcifying environment in CKD induces Wnt signaling in VSMC which in turn contributes to the induction of MMPs which then foster the development of arteriosclerosis. Thus, besides MMP inhibition, the inhibition of Wnt signaling in VSMC might represent a therapeutic target for the prevention of vascular calcifications.

Indexed as

Gene Expression RegulationAnimalsCells, CulturedCell TransdifferentiationDisease Models, AnimalMatrix MetalloproteinasesMiceMuscle, Smooth, VascularReal-Time Polymerase Chain ReactionRNASignal TransductionVascular CalcificationWnt Signaling PathwayMatrix MetalloproteinasesRNAChronic kidney diseaseMatrix metalloproteinasesMOVAS-1Vascular calcificationVascular smooth muscle cellsWnt pathway

Identifiers

PMID27716072
PMCPMC5045611
OpenAlexW2527530755

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.