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

Abstract

A cute myocardial ischemia induces an intense activation of the immune system leading to cytokines and chemokines production 1,2 and to the recruitment of neutrophils and mononuclear cells in the infarcted area.3,4 Early proinflammatory signals are crucial in mediating the response to injury, regulating clearance of dead cardiac myocytes and initiating the cellular events necessary for wound healing. However, optimal healing requires activation of inhibitory mechanisms that suppress cytokine and chemokine synthesis and mediate resolution of the inflammatory infiltrate. Therefore, limiting the inflammatory response amplification seems to be important for containment of injury and optimal infarct healing. Triggering receptor expressed on myeloid cells-1 (TREM-1) is an immune-receptor expressed by neutrophils, macrophages, and mature monocytes that acts as an amplifier of the innate immune response.6 It has been shown that blockade of TREM-1 activation by short inhibitory peptides or fusion protein protected from hyper-responsiveness and death in various models of severe infections.

Prognostic Utility of Soluble TREM‐1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction

“…TREM‐1 is an immune receptor expressed by neutrophils, macrophages, and mature monocytes that acts as an amplifier of proinflammatory innate immune response 9. TREM‐1 connected and regulated complicated signals through several pattern recognition receptors induced by specific toll‐like receptor agonists in the inflammatory process 7, 8. Li et al27 identified that TREM‐1 was a certain epitope of oxidized low‐density lipoprotein in macrophages through the toll‐like receptor pathway, which facilitated foam cell formation and activated inflammatory response, suggesting a crucial role in further plaque progression and rupture.…”

“…Innate immune cells of the neutrophils and monocytes/macrophages are present in the development of atherosclerotic lesions,1, 2, 3 and their activation may contribute significantly to plaque instability 4, 5, 6. Acute myocardial ischemia induces a systemic immediate‐phase response of the immune system, leading to cytokine and chemokine production and to the recruitment of neutrophils and mononuclear cells in the infarcted region of the heart 7, 8…”

“…Furthermore, sTREM‐1 level is identified to be significantly higher in patients with AMI 8. Thus, we performed a large‐scale prospective study to investigate the prognostic utility of sTREM‐1 in patients with AMI.…”

The Biological Basis for Cardiac Repair After Myocardial Infarction

“…Emigrated neutrophils release proteolytic enzymes and contribute to the clearance of the wound from dead cells and matrix debris. Infiltrating neutrophils may also amplify the immune response 148 . Although both in vitro and in vivo experiments have suggested that neutrophils may exert direct cytotoxic actions on viable cardiomyocytes extending ischemic injury 149, 150 , the significance of such effects in the clinical context remains controversial.…”

Chronic Heart Failure and Inflammation

“…72 Many approaches have been successfully used for their ability to limit inflammation and thus minimize cardiac damage and prevent HF development. These range from the blockade of proinflammatory cytokines and chemokines (TNF-α, IL-1β, monocyte chemoattractant protein [MCP] 1), enhancing phagocytosis of dying cells (efferocytosis), inhibition of inflammatory receptors, alterations in the recruitment and expansion of cardiac myeloid cells (monocytes, macrophages, and neutrophils) to stem cell-based therapies, all of which alter net balance between inflammation and repair, setting the trajectory of HF development 20,51,59,[73][74][75][76][77][78][79][80][81] ( Figure 1). …”