Evidence map›Paper›PMID 26265629›Full record

ArticleCirculation research2015

Serine Protease Activation Essential for Endothelial-Mesenchymal Transition in Vascular Calcification.

Jiayi Yao, Pierre J Guihard, Ana M Blazquez-Medela, Yina Guo, Jeremiah H Moon, Medet Jumabay, Kristina I Boström, Yucheng Yao

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

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

72 citing papers in PubMed, 95 citations in OpenAlex.

  1. Review
  2. Article
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  6. Review
  7. COL8A1 regulates endothelial phenotype in inflammatory endothelial-to-mesenchymal transition.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  8. Review
  9. Article
  10. Article
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  14. Collagen VIII in vascular diseases.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Jiayi YaoFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Pierre J GuihardFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Ana M Blazquez-MedelaFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Yina GuoFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Jeremiah H MoonFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Medet JumabayFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Kristina I BoströmFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.).
Yucheng YaoFrom the Division of Cardiology, David Geffen School of Medicine (J.Y., P.J.G., A.M.B.-M., Y.G., J.H.M., M.J., K.I.B., Y.Y.) and The Molecular Biology Institute (K.I.B.), University of California, Los Angeles; and Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China (J.Y.). yyao@mednet.ucla.edu.
Xi'an Jiaotong University · CN

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Molecular Mechanisms of MGP; Role in AVMsR01HL081397 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2006 to 2025
$7.7M
BMP and Notch Crosstalk in Cerebral Arteriovenous MalformationsR01NS079353 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yucheng Yao · 2012 to 2026
$5.3M
Role of The Endothelium In Vascular CalcificationR01HL112839 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOSTROM, KRISTINA I · 2013 to 2016
$1.5M
NHLBI NIH HHS HL112839NHLBI NIH HHS HL30568NHLBI NIH HHS HL81397NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL081397NHLBI NIH HHS R01 HL112839NINDS NIH HHS NS79353NINDS NIH HHS R01 NS079353
6 · The paper itself

Abstract

rationaleEndothelial cells have the ability to undergo endothelial-mesenchymal transitions (EndMTs), by which they acquire a mesenchymal phenotype and stem cell-like characteristics. We previously found that EndMTs occurred in the endothelium deficient in matrix γ-carboxyglutamic acid protein enabling endothelial cells to contribute cells to vascular calcification. However, the mechanism responsible for initiating EndMTs is not fully understood.

objectiveTo determine the role of specific serine proteases and sex determining region Y-box 2 (Sox2) in the initiation of EndMTs. METHODS AND

resultsIn this study, we used in vivo and in vitro models of vascular calcification to demonstrate that serine proteases and Sox2 are essential for the initiation of EndMTs in matrix γ-carboxyglutamic acid protein-deficient endothelium. We showed that expression of a group of specific serine proteases was highly induced in endothelial cells at sites of vascular calcification in Mgp null aortas. Treatment with serine protease inhibitors decreased both stem cell marker expression and vascular calcification. In human aortic endothelial cells, this group of serine proteases also induced EndMTs, and the activation of proteases was mediated by Sox2. Knockdown of the serine proteases or Sox2 diminished EndMTs and calcification. Endothelial-specific deletion of Sox2 decreased expression of stem cell markers and aortic calcification in matrix γ-carboxyglutamic acid protein-deficient mice.

conclusionsOur results suggest that Sox2-mediated activation of specific serine proteases is essential for initiating EndMTs, and thus, may provide new therapeutic targets for treating vascular calcification.

Indexed as

CalcinosisAnimalsCalcium-Binding ProteinsCells, CulturedEndothelium, VascularEnzyme ActivationExtracellular Matrix ProteinsGene Expression ProfilingHumansImmunoblottingKallikreinsMatrix Gla ProteinMesodermMice, Inbred C57BLMice, KnockoutMice, TransgenicCalcium-Binding ProteinsExtracellular Matrix ProteinsKallikreinsMatrix Gla ProteinNuclear ProteinsPancreatic ElastaseSerine EndopeptidasesSox2 protein, mouseSOXB1 Transcription FactorsTwist1 protein, mouseTwist-Related Protein 1endotheliummatrix Gla proteinphenotypeserine proteasesvascular calcification

Identifiers

PMID26265629
PMCPMC4600461
OpenAlexW1945631564

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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.