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

Circ Res. 2015 May 22;116(11):1772-82. doi: 10.1161/CIRCRESAHA.116.305628. Epub 2015 Apr 3.


Rationale: 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 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.

Keywords: immune system; infarction; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Coronary Disease / blood
  • Gene Expression
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / physiopathology
  • Peptides / pharmacology
  • Rats, Wistar
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / blood
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / genetics
  • Ventricular Function, Left / physiology
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / genetics
  • Ventricular Remodeling / physiology


  • Membrane Glycoproteins
  • Peptides
  • Receptors, Immunologic
  • TREM1 protein, human
  • TREM1 protein, mouse
  • Triggering Receptor Expressed on Myeloid Cells-1