Existing users Log In New users Sign up

CCR3 and myocardial infarction

DISCOVERIES (ISSN 2359-7232), 2015, April-June issue


Curaj A, Staudt M, Fatu R, Kraaijeveld AO, Jankowski J, Biessen EAL, Liehn EA. Blockade of CCR3 retains the neutrophils, preserving their survival during healing after myocardial infarction. Discoveries 2015, 3: e45. DOI: 10.15190/d.2015.37

 Submitted: June 20, 2015; Revised: June 29; Accepted: June 30, 2015Published: June 30, 2015;

 GO BACK to 2015, April-June issue


Blockade of CCR3 retains the neutrophils, preserving their survival during healing after myocardial infarction

Adelina Curaj (1,2), Mareike Staudt (1), Roxana Fatu (1), Andreas O. Kraaijeveld (3), Joachim Jankowski (1), Erik A.L. Biessen (4), Elisa A. Liehn (1,*)

(1) Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Germany
(2) Victor Babes National Institute of Pathology, Bucharest, Romania
(3) Department of Cardiology and Einthoven Laboratory of Experimental Vascular Medicine, Leiden University Medical Center, The Netherlands;
(4) Department of Pathology, Academic University Hospital Maastricht, Maastricht, The Netherlands

*Correspondence to: Elisa A. Liehn, MD, PhD, Institute for Molecular Cardiovascular Research, University Hospital Aachen, Germany; Phone: +49-241-80 35983; Fax: +49-241-80 82716; Email: eliehn@ukaachen.de


BACKGROUND: Chemokines are critical mediators in controlling and monitoring the healing and ventricular remodeling after myocardial infarction (MI). They proved to be valuable pharmacological targets for novel therapeutic strategies to reduce the scar formation and to sustain the heart function in patients suffering MI. In the present study, we aim to establish the role of CCR3 in myocardial ischemia/reperfusion.
METHODS AND RESULTS: One week after ischemia/reperfusion induction in a mouse model, the functional and morphological parameters of the heart were analyzed. Isolated-heart perfusion (Langendorff model) showed no significant differences in heart function, infarction size and angiogenesis after pharmacological blockade of CCR3. Notably, a massive neutrophil infiltration was detected in the anti-CCR3 treated group compared to control group. Other immune cells subsets, as well as apoptotic or proliferation signals and collagen synthesis were not affected.
CONCLUSION: Since targeting neutrophils represents one of the most studied therapeutic strategy, this study opens a new perspective for better understanding the physiology and homeostasis of neutrophils, and points out a new research direction which may be of benefit for the patients with myocardial infarction

Access full text of the manuscript here: 


1. Liehn EA, Postea O, Curaj A, Marx N. Repair after myocardial infarction, between fantasy and reality: the role of chemokines. J Am Coll Cardiol. 2011;58:2357-2362.

View article (DOI)  PubMed

2. Kraaijeveld AO, de Jager SC, de Jager WJ, et al. CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms. Circulation. 2007;116:1931-1941.

View article (DOI)  PubMed

3. Ueland T, Nymo SH, Latini R, et al. CCL21 is associated with fatal outcomes in chronic heart failure: data from CORONA and GISSI-HF trials. Eur J Heart Fail. 2013;15:747-755.

View article (DOI)  PubMed

4. Yndestad A, Finsen AV, Ueland T, et al. The homeostatic chemokine CCL21 predicts mortality and may play a pathogenic role in heart failure. PLoS One. 2012;7:e33038.

View article (DOI)  PubMed

5. Kanzler I, Liehn EA, Koenen RR, Weber C. Anti-inflammatory therapeutic approaches to reduce acute atherosclerotic complications. Curr Pharm Biotech. 2012;13:37-45.

View article (DOI)  PubMed

6. White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation--therapeutic opportunities and pharmacological challenges. Pharmacol Rev. 2013;65:47-89.

View article (DOI)  PubMed

7. Liehn EA, Merx MW, Postea O, et al. Ccr1 deficiency reduces inflammatory remodelling and preserves left ventricular function after myocardial infarction. J Cell Mol Med. 2008;12:496-506.

View article (DOI)  PubMed

8. Liehn EA, Tuchscheerer N, Kanzler I, et al. Double-edged role of the CXCL12/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol. 2011;58:2415-2423.

View article (DOI)  PubMed

9. Liehn EA, Kanzler I, Konschalla S, et al. Compartmentalized protective and detrimental effects of endogenous macrophage migration-inhibitory factor mediated by CXCR2 in a mouse model of myocardial ischemia/reperfusion. Arterioscler Thromb Vasc Biol. 2013;33:2180-2186.

View article (DOI)  PubMed

10. Oral H, Kanzler I, Tuchscheerer N, et al. CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction. J Mol Cell Cardiol. 2013;60:1-7.

View article (DOI)  PubMed

11. Dewald O, Zymek P, Winkelmann K, et al. CCL2/Monocyte Chemoattractant Protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ Res. 2005;96:881-889.

View article (DOI)  PubMed

12. Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037-3047.

View article (DOI)  PubMed

13. Braunersreuther V, Pellieux C, Pelli G, et al. Chemokine CCL5/RANTES inhibition reduces myocardial reperfusion injury in atherosclerotic mice. J Mol Cell Cardiol. 2010;48:789-798.

View article (DOI)  PubMed

14. Montecucco F, Braunersreuther V, Lenglet S, et al. CC chemokine CCL5 plays a central role impacting infarct size and post-infarction heart failure in mice. Eur Heart J. 2012;33:1964-1974.

View article (DOI)  PubMed

15. Dobaczewski M, Xia Y, Bujak M, Gonzalez-Quesada C, Frangogiannis NG. CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells. Am J Pathol. 2010;176:2177-2187.

View article (DOI)  PubMed

16. Bonaros N, Sondermeijer H, Schuster M, et al. CCR3- and CXCR4-mediated interactions regulate migration of CD34+ human bone marrow progenitors to ischemic myocardium and subsequent tissue repair. J Thorac Cardiovasc Surg. 2008;136:1044-1053.

View article (DOI)  PubMed

17. Albini A, Ferrini S, Benelli R, et al. HIV-1 Tat protein mimicry of chemokines. Proc Natl Acad Sci U S A. 1998;95:13153-13158.

View article (DOI)  PubMed

18. Daugherty BL, Siciliano SJ, DeMartino JA, et al. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med. 1996;183:2349-2354.

View article (DOI)  PubMed

19. Liehn EA, Piccinini AM, Koenen RR, et al. A new monocyte chemotactic protein-1/chemokine CC motif ligand-2 competitor limiting neointima formation and myocardial ischemia/reperfusion injury in mice. J Am Coll Cardiol. 2010;56:1847-1857.

View article (DOI)  PubMed

20. Frangogiannis NG. Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries. 2015;3:e41.

View article (DOI)

21. Humbles AA, Lu B, Friend DS, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A. 2002;99:1479-1484.

View article (DOI)  PubMed

22. Kanzler I, Tuchscheerer N, Steffens G, et al. Differential roles of angiogenic chemokines in endothelial progenitor cell-induced angiogenesis. Basic Res Cardiol. 2013;108(1):310.

View article (DOI)  PubMed


News & Events Latest news from Discoveries

  • 2018 | For Authors!

    PMC highlighted that a high proportion of authors of Discoveries articles are also members of our Editorial Board. As a result, from now on and for at least 1 year, we will only accept articles from authors that are NOT members of Discoveries' Editorial Board. All articles submitted by our members will be immediately rejected until further notice (one accepted article was already rejected). 

  • 2017-2018 | PubMed inclusion News!

    Discoveries successfully passed the Scientific Quality Review by NLM-NIH for PubMedCentral and PubMed indexing. This is the first and the most important step towards PubMedCentral and PubMed indexing! The second (last) step is the Technical Review.

  • April 2016 | Faster Peer-Review

    Starting on April 13th 2016, all articles selected for a peer-review will receive the post peer-review decision within 10 days. The initial pre-screening time will remain the same (48h from the submission of the manuscript). This decision will significantly accelerate the publication, with no effect on the quality of the peer-review process.

  • February 2016 | Manuscript submission

    Discoveries is commited to excellence, quality and high editorial standards. We are receiving an increasing number of manuscripts for which the identity of the authors/corresponding author can't be verified. Please NOTE that ALL these articles were and will be immediately REJECTED. Indicating an institutional email address is the easiest way to overcome this problem! Moreover, we do not accept any pressure on our editorial board to accept a manuscript. This results in a prompt rejection of the article.

    Editorial Policies
  • January 2016 | Main Objective

    After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles before Discoveries is indexed.

  • August 2015 | Discoveries - on PubMed

    We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded authors) are now processed for being included.

    Discoveries articles now on PubMed
  • April 2015 | Special Issue

    DISCOVERIES published the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

    Special Issue on "Inflammation"
  • 2015 | Ischemia Collection

    DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at info@discoveriesjournals.org

  • September 2014 | Special Issue

    DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled. 

    Special Issue
  • April 2014 | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to Discoveries articles are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | DISCOVERIES

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries. DOI uniquely identifies an article and is provided by CrossRef.

  • July 2013 | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)! There are NO fees for the manuscript submission or publishing of the accepted manuscripts.
    read more

  • July 2013 | DISCOVERIES

    We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim publishing a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...

    read more
Member Login
Free Registration Click here to sign up
Copyright © 2013 Applied Systems. All Rights Reserved.