Inflamm Res. 2025 Dec 27;75(1):9. doi: 10.1007/s00011-025-02168-4.
ABSTRACT
OBJECTIVE: Ischemic heart disease (IHD) is one of the leading causes of death globally, and the process of myocardial repair after myocardial infarction (MI) is complex and crucial. Recent studies have underscored the pivotal role of cardiac-resident macrophages in the salvage of infarcted myocardium. This literature review summarizes recent findings on the central regulatory function of the activating transcription factor 3 (ATF3) in regulating macrophage behavior and macrophage-cardiomyocyte crosstalk during post-MI myocardial repair.
METHODS: A comprehensive review of recent experimental and translational studies was conducted, focusing on ATF3 mediated regulation of macrophage activation, polarization, functional plasticity, and intercellular communication in the context of ischemic heart injury and repair.
RESULTS: ATF3, a stress-responsive transcription factor, is a key mediator in oxidative stress and ischemic injury responses across diverse cellular milieus.The complexity of ATF3's role in regulating macrophage involvement in myocardial repair stems from multiple factors: the cell types expressing ATF3 can affect its function; the stage of disease progression may alter ATF3's role; and ATF3's activity is regulated not only at the expression level but also by post-translational modifications such as ubiquitination and SUMOylation. These factors collectively contribute to the intricate regulation of ATF3. Moreover, the origin of macrophages also dictates their multidimensional role in myocardial repair.
CONCLUSIONS: The ATF3-macrophage axis represents a critical regulatory network in post-MI myocardial repair. Elucidating its context dependent and cell specific mechanisms may provide novel therapeutic insights for modulating post infarction inflammation and improving cardiac repair outcomes.
PMID:41454923 | DOI:10.1007/s00011-025-02168-4