Intercellular communication after myocardial infarction: Macrophage as the centerpiece

Abstract

Post-myocardial infarction (MI) injury, repair, and remodeling are complex biological events orchestrated by the heart and immune cell populations, with immune-inflammation at the core. Macrophages, as the main immune cell population active throughout the post-MI injury to repair processes, are the core of this "drama". Recently, single-cell sequencing and other techniques have revealed the heterogeneity of macrophage origins and the complexity of macrophage subpopulation transformation and intercellular communication after MI. Defining the changes in macrophage subpopulation dynamics and macrophage-centered intercellular communication after MI may represent new targeted therapeutic strategies. It also helps to select the optimal time point for anti-inflammatory or pro-repair accurately. Therefore, in this review, we summarize the major macrophage subpopulations active at different times after MI and their functional characteristics based on gene expression profiles. Meanwhile, we summarize macrophage-centered intercellular communication, focusing on how macrophages interact with cardiomyocytes, neutrophils, fibroblasts, endothelial cells, and other cardiac cells. Together, these dominate the transition from inflammatory injury to fibrotic repair in the infarcted heart. We also focus on the regulatory potential of immune metabolism in macrophage subpopulation transformation and intercellular communication after MI, particularly providing new insights about lactylation. We conclude by emphasizing macrophage-centric targeting strategies and clinical translational potential, to provide ideas for the clinical treatment of MI.

Keywords: Immunometabolism; Intercellular communication; Macrophages; Myocardial infarction; Subpopulation shift; Therapeutic strategies.