Evidence map›Paper›PMID 24950695›Full record

ArticleEuropean heart journal2015

Silencing of CCR2 in myocarditis.

Florian Leuschner, Gabriel Courties, Partha Dutta, Luke J Mortensen, Rostic Gorbatov, Brena Sena, Tatiana I Novobrantseva, Anna Borodovsky, Kevin Fitzgerald, Victor Koteliansky and 12 more

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

Article in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
4.3field-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

91 citing papers in PubMed, 153 citations in OpenAlex.

  1. Immune checkpoint inhibitor-associated myocarditis: clinical and mechanistic insights.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. RNA Therapeutics in Heart Failure.Journal of cardiovascular translational research · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 8 institutions in 2 countries.

Florian LeuschnerCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg D-69120, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany mnahrendorf@mgh.harvard.edu florian.leuschner@med.uni-heidelberg.de.
Gabriel CourtiesCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Partha DuttaCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Luke J MortensenCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Rostic GorbatovCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Brena SenaCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Tatiana I NovobrantsevaAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Anna BorodovskyAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Kevin FitzgeraldAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Victor KotelianskyDepartment of Chemical Engineering, Massachusetts Institute of Technology, University Hospital Heidelberg, Heidelberg, Germany.
Yoshiko IwamotoCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Marina BohlenderDepartment of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg D-69120, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Soeren MeyerDepartment of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg D-69120, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Felix LasitschkaInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg 69120, Germany.
Benjamin MederDepartment of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg D-69120, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Hugo A KatusDepartment of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg D-69120, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Charles LinCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Peter LibbyCardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Filip K SwirskiCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
Daniel G AndersonDepartment of Chemical Engineering, Massachusetts Institute of Technology, University Hospital Heidelberg, Heidelberg, Germany David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA Division of Health Science Technology, Massachusetts Institute of Technology, Boston, MA, USA Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Boston, MA, USA.
Ralph WeisslederCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Matthias NahrendorfCenter for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA mnahrendorf@mgh.harvard.edu florian.leuschner@med.uni-heidelberg.de.
Center for Systems Biology · USHarvard University · USUniversity Hospital Heidelberg · DEAlnylam Pharmaceuticals (United States) · USMassachusetts General Hospital · USMassachusetts Institute of Technology · USBrigham and Women's Hospital · USGerman Centre for Cardiovascular Research · DE

Funding

Imaging of Cardiac Transplant RejectionR01HL095629 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NAHRENDORF, MATTHIAS · 2009 to 2013
$2.2M
Cell-Cell Interaction in Heart FailureR01HL117829 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NAHRENDORF, MATTHIAS · 2014 to 2017
$1.7M
Pathogen specific imaging of endocarditisR01HL114477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NAHRENDORF, MATTHIAS, PANIZZI, PETER ROLF · 2013 to 2016
$1.7M
Effect of diabetes on myelopoiesis and atherosclerosisK99HL121076 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI DUTTA, PARTHA · 2014 to 2015
$273k
NHLBI NIH HHS HHSN268201000044CNHLBI NIH HHS K99 HL121076NHLBI NIH HHS R01 HL095629NHLBI NIH HHS R01-HL095629NHLBI NIH HHS R01 HL114477NHLBI NIH HHS R01-HL114477NHLBI NIH HHS R01-HL117829
6 · The paper itself

Abstract

backgroundMyocarditis is characterized by inflammatory cell infiltration of the heart and subsequent deterioration of cardiac function. Monocytes are the most prominent population of accumulating leucocytes. We investigated whether in vivo administration of nanoparticle-encapsulated siRNA targeting chemokine (C-C motif) receptor 2 (CCR2)-a chemokine receptor crucial for leucocyte migration in humans and mice--reduces inflammation in autoimmune myocarditis. METHODS AND

resultsIn myocardium of patients with myocarditis, CCL2 mRNA levels and CCR2(+) cells increased (P < 0.05), motivating us to pursue CCR2 silencing. Flow cytometric analysis showed that siRNA silencing of CCR2 (siCCR2) reduced the number of Ly6C(high) monocytes in hearts of mice with acute autoimmune myocarditis by 69% (P < 0.05), corroborated by histological assessment. The nanoparticle-delivered siRNA was not only active in monocytes but also in bone marrow haematopoietic progenitor cells. Treatment with siCCR2 reduced the migration of bone marrow granulocyte macrophage progenitors into the blood. Cellular magnetic resonance imaging (MRI) after injection of macrophage-avid magnetic nanoparticles detected myocarditis and therapeutic effects of RNAi non-invasively. Mice with acute myocarditis showed enhanced macrophage MRI contrast, which was prevented by siCCR2 (P < 0.05). Follow-up MRI volumetry revealed that siCCR2 treatment improved ejection fraction (P < 0.05 vs. control siRNA-treated mice).

conclusionThis study highlights the importance of CCR2 in the pathogenesis of myocarditis. In addition, we show that siCCR2 affects leucocyte progenitor trafficking. The data also point to a novel therapeutic strategy for the treatment of myocarditis.

Indexed as

AdultAnimalsAutoimmune DiseasesCell MovementChemokine CCL2FemaleHematopoietic Stem CellsHumansMagnetic Resonance AngiographyMaleMiceMonocytesMyocarditisNanoparticlesRNA InterferenceRNA, Small InterferingChemokine CCL2RNA, Small InterferingInflammationMolecular imagingMyocarditisNanoparticlesiRNA

Identifiers

PMID24950695
PMCPMC4465633
OpenAlexW2163857843

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.