Evidence map›Paper›PMID 30826357›Full record

ArticleEBioMedicine2019

Proteomics based identification of KDM5 histone demethylases associated with cardiovascular disease.

Marika Mokou, Julie Klein, Manousos Makridakis, Vasiliki Bitsika, Jean-Loup Bascands, Jean Sebastien Saulnier-Blache, William Mullen, Michael Sacherer, Jerome Zoidakis, Burkert Pieske and 4 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

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  12. Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.International journal of molecular sciences · 2024
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  17. MicroRNAs as therapeutic targets in cardiovascular disease.The Journal of clinical investigation · 2022
    Review
  18. APEX2-Mediated Proximity Labeling Resolves the DDIT4-Interacting Proteome.International journal of molecular sciences · 2022
    Article
  19. 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 9 institutions in 6 countries.

Marika MokouBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Biology, University of Athens, School of Medicine, Athens, Greece.
Julie KleinInstitut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France.
Manousos MakridakisBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Vasiliki BitsikaBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Jean-Loup BascandsINSERM, U1188, Sainte Clotilde, La Réunion, France; Université de La Réunion, Sainte Clotilde, La Réunion, France.
Jean Sebastien Saulnier-BlacheInstitut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France.
William MullenBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Michael SachererDepartment of Cardiology, Medical University of Graz, Graz, Austria.
Jerome ZoidakisBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Burkert PieskeDepartment of Internal Medicine and Cardiology, Charité University Medicine, Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Berlin, Germany; Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany; Berlin Institute of Health (BIH), Germany.
Harald MischakBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Mosaiques Diagnostics GmbH, Hannover, Germany.
Maria G RoubelakisLaboratory of Biology, University of Athens, School of Medicine, Athens, Greece.
Joost P SchanstraInstitut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier Toulouse, Toulouse, France. Electronic address: joost-peter.schanstra@inserm.fr.
Antonia VlahouBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. Electronic address: vlahoua@bioacademy.gr.
Biomedical Research Foundation of the Academy of Athens · GRUniversité Toulouse III - Paul Sabatier · FRNational and Kapodistrian University of Athens · GRAcademy of Athens · GRDeutsches Herzzentrum der Charité · DEInserm · FRMedical University of Graz · ATMosaiques Diagnostics and Therapeutics (Germany) · DEUniversity of Glasgow · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe increased prevalence of cardiovascular disease (CVD) indicates a demand for novel therapeutic approaches. Proteome analysis of vascular tissues from animal models and humans with CVD could lead to the identification of novel druggable targets.

methodsLC-MS/MS analysis of thoracic aortas from three mouse models of non-diabetic and diabetic (streptozotocin (STZ)-induced) atherosclerosis followed by bioinformatics/pathway analysis was performed. Selected findings were confirmed by proteomics analysis of human vessels from patients with CVD as well as in vitro studies (migration, proliferation, angiogenesis assays) using endothelial (HUVEC) cells.

findingsComparative tissue proteomics of low density lipoprotein receptor deficient (Ldlr-/-) and diabetic Ldlr-/- (Ldlr-/-STZ) with wild type (WT) animals led to the identification of 284 differentially expressed proteins in both models. Among them, 177 proteins were also differentially expressed in diabetic apolipoprotein E deficient (ApoE-/-STZ) mice, suggesting expression changes associated with atherosclerosis independent of the model used. These proteins recapitulated the hallmarks of atherosclerosis. Comparison of these findings with differentially expressed proteins in human vessels with CVD enabled shortlisting of six commonly dysregulated proteins. Among them, lysine-specific demethylase 5D (KDM5D) exhibited pronounced overexpression accompanied by a reduction in the protein levels of its substrate, the trimethylated lysine 4 of histone H3 (H3K4me3), in patients with CVD. Functional interference studies applying a KDM5 inhibitor on HUVEC reduced cell proliferation, migration and tube-forming ability in vitro.

interpretationThis high-throughput proteomics strategy identified KDM5 histone demethylases being potentially involved in CVD, possibly by affecting H3K4 methylation. FUND: [SysVasc, HEALTH-2013 603288], [ERA-CVD PROACT: ANR-17-ECVD-0006, 01KL1805], [FRM, DEQ20170336759].

Indexed as

AnimalsAtherosclerosisDiabetic CardiomyopathiesHistone DemethylasesHumansHuman Umbilical Vein Endothelial CellsMaleMass SpectrometryMiceMice, Inbred C57BLMinor Histocompatibility AntigensProteinsProteomicsHistone DemethylasesKDM5D protein, humanKdm5d protein, mouseMinor Histocompatibility AntigensProteinsAtherosclerosisCardiovascular diseaseDiabetesH3K4KDM5Proteomics

Identifiers

PMID30826357
PMCPMC6443027
OpenAlexW2919441515

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.