The Protective Role of TREM2 in the Heterogenous Population of Macrophages during Post-Myocardial Infarction Inflammation

• Published in: International journal of molecular sciences 2023-03, Vol.24 (6), p.5556
• Main Authors: Kim, Sang Hyun, Lee, Kwan Yong, Chang, Kiyuk
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis; Cardiomyocytes; Cardiovascular disease; Chemokines; Clinical outcomes; Congestive heart failure; Cytokines; Disease Models, Animal; Genotype & phenotype; Health aspects; Heart; Heart attack; Heart attacks; Heterogeneity; Immune system; Inflammation; Inflammation - metabolism; Ischemia; Ligands; Lymphocytes; macrophage; Macrophages; Macrophages - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Monoclonal antibodies; monocyte; Monocytes; Myocardial infarction; Myocardial Infarction - metabolism; Myocardium; Myocardium - metabolism; Neutrophils; Pathogenesis; Population studies; protective inflammatory; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Recruitment; Review; Therapeutic targets; Transcriptomics; TREM2; Ventricle; Ventricular Remodeling - genetics; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065556

Advances in interventions after myocardial infarction (MI) have dramatically increased survival, but MI remains the leading cause of heart failure due to maladaptive ventricular remodeling following ischemic damage. Inflammation is crucial in both the initial response to ischemia and subsequent wound healing in the myocardium. To date, preclinical and clinical efforts have been made to elucidate the deleterious effects of immune cells contributing to ventricular remodeling and to identify therapeutic molecular targets. The conventional concept classifies macrophages or monocytes into dichotomous populations, while recent studies support their diverse subpopulations and spatiotemporal dynamicity. The single-cell and spatial transcriptomic landscapes of macrophages in infarcted hearts successfully revealed the heterogeneity of cell types and their subpopulations post-MI. Among them, subsets of Trem2 macrophages were identified that were recruited to infarcted myocardial tissue in the subacute phase of MI. The upregulation of anti-inflammatory genes was observed in Trem2 macrophages, and an in vivo injection of soluble Trem2 during the subacute phase of MI significantly improved myocardial function and the remodeling of infarcted mice hearts, suggesting the potential therapeutic role of Trem2 in LV remodeling. Further investigation of the reparative role of Trem2 in LV remodeling would provide novel therapeutic targets for MI.