A New Monocyte Chemotactic Protein-1/Chemokine CC Motif Ligand-2 Competitor Limiting Neointima Formation and Myocardial Ischemia/Reperfusion Injury in Mice

Liehn, Elisa A.; Piccinini, Anna M.; Koenen, Rory R.; Soehnlein, Oliver; Adage, Tiziana; Fatu, Roxana; Curaj, Adelina; Popescu, Alexandra; Zernecke, Alma; Kungl, Andreas J.; Weber, Christian

doi:10.1016/j.jacc.2010.04.066

Cited by 106 publications

(89 citation statements)

References 44 publications

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“…The chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) axis controls Ly6Chi monocyte infiltration in the infarcted myocardium, and several studies using genetic or pharmacological approaches have shown that disruption of CCL2/CCR2 signaling alleviates adverse LV remodeling after MI through the inhibition of inflammatory cell recruitment. [5][6][7] In addition, expression of other CC-chemokines in the ischemic heart, such as CCL5 or CCL3, 8 has been associated with excessive inflammation and poor LV remodeling.…”

mentioning

confidence: 99%

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

Cochain

Auvynet

Poupel

et al. 2012

ATVB

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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.

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confidence: 99%

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

Cochain

Auvynet

Poupel

et al. 2012

ATVB

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“…Applying a rational design approach based the CellJammer ® Technology [29] human proinflammatory CCL2 was turned into an anti-inflammatory chemokine decoy CCL2 was altered to an anti-inflammatory chemokine decoy protein with increased glycan binding affinity, as previously reported by Piccinini et al [30] and was shown to limit neointima formation and myocardial ischemia/ reperfusion injury in mice [31].…”

Section: Ms Is An Inflammatory Disease Of the Central Nervous System mentioning

confidence: 87%

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

Gschwandtner

Piccinini

Gerlza

et al. 2016

Neuroscience Letters

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“…Notably, mice with genetic inactivation of MCP-1 and its CC-chemokine receptor 2 (CCR2) are particularly resistant to atherosclerosis [9]. An MCP-1 competitor, that inhibits monocyte chemotaxis or transendothelial migration, also reduces inflammatory monocyte recruitment, limits neo-intimal hyperplasia and attenuates myocardial ischemiareperfusion injury in mice [29]. MCP-1 is also the most increased pro-inflammatory parameter in obese children compared to lean ones and correlates positively with the degree of obesity [13,30].…”

Section: Statins and Inflammatory Parametersmentioning

confidence: 99%

Randomized Study of the Effects of Statin on Inflammatory and Prothrombotic States in Obese Adolescents

Dirlewanger¹,

P²,

Roux‐Lombard³

et al. 2016

Journal of Paediatrics and Neonatal Disorders

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Background: Increased inflammatory cytokines, C-reactive protein (CRP) and prothrombotic parameters are potential markers of cardiovascular risks in childhood obesity. Objectives:We investigated whether a statin treatment can reverse these early cardiovascular risk indicators. The primary outcome was the effect of sixteen weeks of statins on the inflammatory cytokines, CRP and the pro-thrombotic state in obese adolescents. Methods:This randomized controlled double-blind study conducted at the University Hospital of Geneva included 28 obese adolescents aged 12-16 years. Subjects received either placebo (P) or atorvastatin (A) for sixteen weeks. Levels of monocyte chemoattractant protein 1 (MCP-1), interleukin-6, interferon-γ-inducible protein, interleukin-10, interleukin-1 receptor antagonist and CRP were measured at baseline, after sixteen weeks and after one year. Coagulation parameters were evaluated by prothrombin time, activated partial thromboplastin time, fibrinogen levels and endogenous thrombin potential (ETP) at each visit. Results:The MCP-1 level was stable in group A after sixteen weeks of treatment, while it tended to increase in group P (median evolution, 0.2 pg/mL in A vs 34.3 pg/mL in P). The ETP levels decreased in group A and increased in group P (median evolution, -7.0 mA in A vs 12.9 mA in P). These differences of the evolution were not statistically different (MCP-1 p= 0.09, ETP p= 0.07), but after adjustment for age and BMI the ETP evolution reached significance (ETP adjusted, p=0.01). The baseline fibrinogen levels were already high in both groups (median 3.6 g/L, norm < 3.0). No prolonged effects were detected after one year. Conclusions: Increased levels of fibrinogen are already observed in obese adolescents reflecting the procoagluant risk. ETP decreased significantly with atorvastatin treatment in comparison to the non-treated group. Atorvastatin did however not decrease inflammation parameters. Abstract Randomized Study of the Effects of Statin on Inflammatory and Prothrombotic States in Obese Adolescents

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A New Monocyte Chemotactic Protein-1/Chemokine CC Motif Ligand-2 Competitor Limiting Neointima Formation and Myocardial Ischemia/Reperfusion Injury in Mice

Cited by 106 publications

References 44 publications

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

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

Interfering with the CCL2–glycosaminoglycan axis as a potential approach to modulate neuroinflammation

Randomized Study of the Effects of Statin on Inflammatory and Prothrombotic States in Obese Adolescents

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