The Chemokine Decoy Receptor D6 Prevents Excessive Inflammation and Adverse Ventricular Remodeling After Myocardial Infarction

被引：84

作者：

Cochain, Clement ^{[1
]}

Auvynet, Constance ^{[2
]}

Poupel, Lucie ^{[2
]}

Vilar, Jose ^{[1
]}

Dumeau, Edouard ^{[1
]}

Richart, Adele ^{[1
]}

Recalde, Alice ^{[1
]}

Zouggari, Yasmine ^{[1
]}

Yin, Kiave Yune Ho Wang ^{[1
]}

Bruneval, Patrick ^{[3
]}

Renault, Gilles

Marchiol, Carmen

Bonnin, Philippe ^{[5
]}

Levy, Bernard ^{[1
]}

Bonecchi, Raffaella ^{[6
,7
]}

Locati, Massimo ^{[6
,7
]}

Combadiere, Christophe ^{[2
]}

Silvestre, Jean-Sebastien ^{[1
,4
]}

机构：

[1] Univ Paris 05, INSERM, Paris Cardiovasc Res Ctr, UMR S970,Hop Europeen Georges Pompidou, F-75015 Paris, France

[2] UPMC Univ Paris 06, Hop La Pitie Salpetriere, INSERM, UMR S945,Lab Immun & Infect, Paris, France

[3] Hop Europeen Georges Pompidou, Serv Anat Pathol, Paris, France

[4] Univ Paris 05, INSERM, Paris Cardiovasc Res Ctr, U970, F-75015 Paris, France

[5] Univ Paris 07, AP HP, Paris, France

[6] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy

[7] Humanitas Clin & Res Ctr, Milan, Italy

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2012年 / 32卷 / 09期

关键词：

chemokines; immune system; inflammation; ischemic heart disease; leukocytes; ZINC-FINGER PROTEIN; OXIDATIVE STRESS; MICE; DYSFUNCTION; EXPRESSION; INDUCTION; SUBSET; DEATH; MCPIP;

D O I：

10.1161/ATVBAHA.112.254409

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2012;32:2206-2213.)

引用

页码：2206 / +

页数：14

共 25 条

[1]

Bonecchi R, 1999, J IMMUNOL, V162, P474

[2]

Mechanical ventricular assistance in heart failure: pathology of the cardiac apex removed during device implantation [J].