| First Author | Boufenzer A | Year | 2015 |
| Journal | Circ Res | Volume | 116 |
| Issue | 11 | Pages | 1772-82 |
| PubMed ID | 25840803 | Mgi Jnum | J:249177 |
| Mgi Id | MGI:6098966 | Doi | 10.1161/CIRCRESAHA.116.305628 |
| Citation | Boufenzer A, et al. (2015) TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction. Circ Res 116(11):1772-82 |
| abstractText | 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. |
