Macrophage Plasticity and Immune Remodeling in Ischemic Heart Failure.

摘要

Macrophages, as central effectors of innate immunity, play context-specific and time-dependent roles in myocardial infarction (MI) and in the pathogenesis of ischemic heart failure (HF). Their plasticity, heterogeneity, and interactions with other cardiac and immune cells determine whether inflammation resolves and repair ensues, or maladaptive remodeling culminates in ventricular dysfunction. In this review, we synthesize findings from lineage-tracing studies, single-cell transcriptomic atlases, and clinical trials to highlight macrophage ontogeny, recruitment, reparative programs, and pathogenic functions in chronic remodeling. We discuss embryonically-derived cardiac resident macrophages, recruitment of monocyte-derived macrophages and their respective roles after ischemic injury, and how efferocytotic clearance of cellular and mitochondrial debris is a key component of the reparative response. We highlight macrophage interactions with cardiomyocytes, fibroblasts, neutrophils, T cells, and conduction system cells, and outline translational strategies involving chemokine pathway inhibition and specialized pro-resolving mediators. Mechanistic insight into macrophage ontogeny, heterogeneity, and intercellular interactions has uncovered novel therapeutic possibilities. Targeted, temporally staged macrophage therapies, using biomarkers and imaging for patient stratification, may improve post-MI healing and prevent progression toward ischemic HF.