title: TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction.
abstract: BACKGROUND
  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.
  
  
  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 TREM-1 (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.
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Amir
authors.initials: A
authors.lastname: Boufenzer
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Jérémie
authors.initials: J
authors.lastname: Lemarié
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Youcef
authors.initials: Y
authors.lastname: Bouazza
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Fatiha
authors.initials: F
authors.lastname: Maskali
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Frédérique
authors.initials: F
authors.lastname: Groubatch
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Claire
authors.initials: C
authors.lastname: Bastien
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Marie
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Raphael
authors.initials: R
authors.lastname: Cohen
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Danchin
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.).
authors.forename: Hafid
authors.initials: H
authors.lastname: Ait-Oufella
authors.affiliation: From the Inserm UMR_S1116 (A.B., J.L., M.D., Y.B., S.G.) and School of Surgery (N. T., F. G.), Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France; Medical Intensive Care Unit, Hôpital Central (J.L., S.G.), Nancyclotep, Hôpital Brabois (F.M., P.-Y.M.), and Department of Pathology, Hôpital Brabois (C.B.), CHU Nancy, Nancy, France; Assistance Publique Hôpitaux de Paris (APHP), Department of Clinical Pharmacology, URC-EST, Hôpital Saint-Antoine, Paris, France (T.S.); UPMC University Paris 06, Paris, France (T.S.); INOTREM SA, Nancy, France (M.D.); Inserm U965, Paris, France (P.B.); Paris Cardiovascular Research Center, Inserm U970, Paris, France (P. B., R.C., J.-S.S., H.A.-O.); APHP, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France (N.D.); and Université Paris-Descartes, Paris, France (N.D.). s.gibot@chu-nancy.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D003327:Coronary Disease / Q000097:blood; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D010455:Peptides; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: immune system; infarction; inflammation