Evidence map›Paper›PMID 26113265›Full record

ArticleCardiovascular research2015

Citrullination of myofilament proteins in heart failure.

Justyna Fert-Bober, John T Giles, Ronald J Holewinski, Jonathan A Kirk, Helge Uhrigshardt, Erin L Crowgey, Felipe Andrade, Clifton O Bingham, Jin Kyun Park, Marc K Halushka and 3 more

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In one paragraph

Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Is a decline in myocardial citrullination in the aged female heart really PAD2 the bone?American journal of physiology. Heart and circulatory physiology · 2025
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Proteomics of the heart.Physiological reviews · 2024
    Review
  11. DCM-Spheroid Morphs Express PADs and Citrullinated Cytoskeletal Proteins.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024
    Article
  12. Article
  13. GnRH Induces Citrullination of the Cytoskeleton in Murine Gonadotrope Cells.International journal of molecular sciences · 2024
    Article
  14. Review
  15. Characterizing citrullination by mass spectrometry-based proteomics.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  16. Article
  17. Article
  18. Article
  19. Citrullination is linked to reduced CaActa physiologica (Oxford, England) · 2022
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Justyna Fert-BoberThe Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Advanced Clinical BioSystems Research Institute, Advanced Health Science Building, 9229, Los Angeles, CA, USA Bayview Proteomics Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA Justyna.Fert-Bober@cshs.org.
John T GilesDivision of Rheumatology, Department of Medicine, Columbia University, New York, NY, USA.
Ronald J HolewinskiThe Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Advanced Clinical BioSystems Research Institute, Advanced Health Science Building, 9229, Los Angeles, CA, USA.
Jonathan A KirkDivision of Cardiology, Department of Medicine, The Johns Hopkins University Medical Institutions, Baltimore, MD, USA.
Helge UhrigshardtBayview Proteomics Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Erin L CrowgeyThe Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Advanced Clinical BioSystems Research Institute, Advanced Health Science Building, 9229, Los Angeles, CA, USA.
Felipe AndradeDivision of Cardiology, Department of Medicine, The Johns Hopkins University Medical Institutions, Baltimore, MD, USA.
Clifton O BinghamDivision of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA Division of Rheumatology, Department of Medicine, Seoul National University Hospital, Seoul, Korea.
Jin Kyun ParkDivision of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA Division of Rheumatology, Department of Medicine, Seoul National University Hospital, Seoul, Korea.
Marc K HalushkaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David A KassDivision of Cardiology, Department of Medicine, The Johns Hopkins University Medical Institutions, Baltimore, MD, USA.
Joan M BathonDivision of Rheumatology, Department of Medicine, Columbia University, New York, NY, USA.
Jennifer E Van EykThe Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Advanced Clinical BioSystems Research Institute, Advanced Health Science Building, 9229, Los Angeles, CA, USA Bayview Proteomics Center, Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USJohns Hopkins Bayview Medical Center · USCedars-Sinai Medical Center · USColumbia University · USSeoul National University Hospital · KR

Funding

Pathobiology of Cardiac Dyssynchrony &ResynchronizationP01HL077180 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KASS, DAVID ALAN · 2004 to 2014
$22.8M
NHLBI NIH HHS HHSN268201000032CNHLBI NIH HHS P01 HL077180
6 · The paper itself

Abstract

aimsCitrullination, the post-translational conversion of arginine to citrulline by the enzyme family of peptidylarginine deiminases (PADs), is associated with several diseases, and specific citrullinated proteins have been shown to alter function while others act as auto-antigens. In this study, we identified citrullinated proteins in human myocardial samples, from healthy and heart failure patients, and determined several potential functional consequences. Further we investigated PAD isoform cell-specific expression in the heart. METHODS AND

resultsA citrullination-targeted proteomic strategy using data-independent (SWATH) acquisition method was used to identify the modified cardiac proteins. Citrullinated-induced sarcomeric proteins were validated using two-dimensional gel electrophoresis and investigated using biochemical and functional assays. Myocardial PAD isoforms were confirmed by RT-PCR with PAD2 being the major isoform in myocytes. In total, 304 citrullinated sites were identified that map to 145 proteins among the three study groups: normal, ischaemia, and dilated cardiomyopathy. Citrullination of myosin (using HMM fragment) decreased its intrinsic ATPase activity and inhibited the acto-HMM-ATPase activity. Citrullinated TM resulted in stronger F-actin binding and inhibited the acto-HMM-ATPase activity. Citrullinated TnI did not alter the binding to F-actin or acto-HMM-ATPase activity. Overall, citrullination of sarcomeric proteins caused a decrease in Ca(2+) sensitivity in skinned cardiomyocytes, with no change in maximal calcium-activated force or hill coefficient.

conclusionCitrullination unique to the cardiac proteome was identified. Our data indicate important structural and functional alterations to the cardiac sarcomere and the contribution of protein citrullination to this process.

Indexed as

Adenosine TriphosphatasesAnimalsAnimals, NewbornCitrullineCytoskeletal ProteinsHeart FailureHumansHydrolasesMaleMass SpectrometryMice, Inbred C57BLMyocardiumMyofibrilsMyosin SubfragmentsProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2Adenosine TriphosphatasesCitrullineCytoskeletal ProteinsHydrolasesMyosin SubfragmentsPADI2 protein, humanProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 2ProteomeCitrullinationHeart failureMyofilamentPeptidylarginine deiminasesSarcomere

Identifiers

PMID26113265
PMCPMC4614685
OpenAlexW2144701759

What OpenQuestion holds

Textmetadata
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.