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.).
Circ Res. 2015 May 22;116(11):1772-82. doi: 10.1161/CIRCRESAHA.116.305628. Epub 2015 Apr 3.
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.
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.
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.
These data suggest that TREM-1 could constitute a new therapeutic target during acute MI.
心肌梗死（MI）后的最佳转归取决于协调的愈合反应，其中清除碎片和修复心肌细胞外基质都起着主要作用。然而，不良的重构和过度的炎症会促进心力衰竭，使白细胞成为 MI 后组织修复和伤口愈合的核心主角和潜在治疗靶点。
在这项研究中，我们研究了触发受体表达在髓样细胞-1（TREM-1）在协调 MI 后炎症反应中的作用。TREM-1 由中性粒细胞和成熟单核细胞表达，是先天免疫反应的放大器。
在梗塞后，TREM-1 在小鼠和人类缺血心肌中的表达上调。Trem-1 基因无效或使用合成肽（LR12）抑制可抑制心肌炎症，限制中性粒细胞募集和单核细胞趋化蛋白-1 的产生，从而减少经典单核细胞向心脏的动员。它还改善了小鼠的左心室功能和存活率（每组 20-22 只）。在永久性和短暂性心肌缺血期间，Trem-1 阻断也改善了心脏功能并限制了心室重构，如氟脱氧葡萄糖正电子发射断层扫描成像和电导导管研究所示（每组 9-18 只）。TREM-1 激活的标志物可溶性 TREM-1（sTREM-1）可在急性 MI 患者的血浆中检测到（n=1015），其浓度是死亡的独立预测因子。
这些数据表明，TREM-1 可能成为急性 MI 期间的一个新的治疗靶点。
