Document Detail

The Chemokine Decoy Receptor D6 Prevents Excessive Inflammation and Adverse Ventricular Remodeling After Myocardial Infarction.
MedLine Citation:
PMID:  22796582     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming infiltration of innate immune cells has been shown to promote adverse remodeling and cardiac rupture. Recruitment of inflammatory cells in the ischemic heart depends highly on the family of CC-chemokines and their receptors. Here, we hypothesized that the chemokine decoy receptor D6, which specifically binds and scavenges inflammatory CC-chemokines, might limit inflammation and adverse cardiac remodeling after infarction. METHODS AND RESULTS: D6 was expressed in human and murine infarcted myocardium. In a murine model of myocardial infarction, D6 deficiency led to increased chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 3 levels in the ischemic heart. D6-deficient (D6(-/-)) infarcts displayed increased infiltration of pathogenic neutrophils and Ly6Chi monocytes, associated with strong matrix metalloproteinase-9 and matrix metalloproteinase-2 activities in the ischemic heart. D6(-/-) mice were cardiac rupture prone after myocardial infarction, and functional analysis revealed that D6(-/-) hearts had features of adverse remodeling with left ventricle dilation and reduced ejection fraction. Bone marrow chimera experiments showed that leukocyte-borne D6 had no role in this setting, and that leukocyte-specific chemokine (C-C motif) receptor 2 deficiency rescued the adverse phenotype observed in D6(-/-) mice. CONCLUSIONS: We show for the first time that the chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction.
Clément Cochain; Constance Auvynet; Lucie Poupel; José Vilar; Edouard Dumeau; Adèle Richart; Alice Récalde; Yasmine Zouggari; Kiave Yune Ho Wang Yin; Patrick Bruneval; Gilles Renault; Carmen Marchiol; Philippe Bonnin; Bernard Lévy; Raffaella Bonecchi; Massimo Locati; Christophe Combadière; Jean-Sébastien Silvestre
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-12
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Université Paris Descartes, INSERM UMR-S970, Paris Cardiovascular Research Center, Hôpital Européen Georges Pompidou.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Simvastatin Reduces Myocardial Injury Undergoing Noncoronary Artery Cardiac Surgery: A Randomized Co...
Next Document:  Cognitive-behavioural therapy reduces unwanted thought intrusions in generalized anxiety disorder.