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TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction

By Amir Boufenzer, Jeremie Lemarie, Tabassome Simon, Marc Derive, Youcef Bouazza, Nguyen Tran, Fatiha Maskali, Frederique Groubatch, Philippe Bonnin, Claire Bastien, Patrick Bruneval, Pierre-Yves Marie, Raphael Cohen, Nicolas Danchin, Jean-Sébastien Silvestre, Hafid Ait-Oufella and Sébastien Gibot

Abstract

International audienceRationale: Optimal outcome after myocardial infarction (MI) depends on a coordinated healing response in which both debris removal and repair of the myocardial extracellular matrix play a major role. However, adverse remodeling and excessive inflammation can promote heart failure, positioning leucocytes as central protagonists and potential therapeutic targets in tissue repair and wound healing after MI. Objective: In this study, we examined the role of triggering receptor expressed on myeloid cells-1(TREM-1) in orchestrating the inflammatory response that follows MI. TREM-1, expressed by neutrophils and mature monocytes, is an amplifier of the innate immune response. Methods and Results: After infarction, TREM-1 expression is upregulated in ischemic myocardium in mice and humans. Trem-1 genetic invalidation or pharmacological inhibition using a synthetic peptide (LR12) dampens myocardial inflammation, limits neutrophils recruitment and monocyte chemoattractant protein-1 production, thus reducing classical monocytes mobilization to the heart. It also improves left ventricular function and survival in mice (n=20-22 per group). During both permanent and transient myocardial ischemia, Trem-1 blockade also ameliorates cardiac function and limits ventricular remodeling as assessed by fluorodeoxyglucose-positron emission tomographic imaging and conductance catheter studies (n=9-18 per group). The soluble form of TREM1 (sTREM-1), a marker of TREM-1 activation, is detectable in the plasma of patients having an acute MI (n=1015), and its concentration is an independent predictor of death. Conclusions: These data suggest that TREM-1 could constitute a new therapeutic target during acute MI

Topics: infarction, inflammation, immune system, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Publisher: American Heart Association
Year: 2015
DOI identifier: 10.1161/CIRCRESAHA.116.305628
OAI identifier: oai:HAL:hal-01514439v1
Provided by: Hal-Diderot
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