Macrophages in Septic Cardiomyopathy: Heterogeneity, Function, and Therapy

Sepsis is a life-threatening condition characterized by multiple organ dysfunction resulting from a dysregulated host immune response to infection. Septic cardiomyopathy (SCM), one of the most severe complications of sepsis, manifests as myocardial tissue injury and functional impairment and serves as a primary contributor to mortality in septic patients. Macrophages, pivotal innate immune cells in the heart, are classified into distinct subsets based on their developmental origins and microenvironmental cues. The dual roles of macrophage subsets, mediating both injury and protection, during the pathogenesis of SCM remain under active investigation. This review delineates the heterogeneity of macrophage subsets in sepsis and their cardiac implications, with a focus on elucidating the molecular mechanisms underlying macrophage-mediated cardiac injury (e.g., secretion of myocardial depressant substances, inflammatory responses, induction of mitochondrial dysfunction, mediation of ferroptosis) and protective processes (e.g., anti-inflammatory responses, phagocytic repair). These insights aim to provide a theoretical foundation for developing targeted immunomodulatory therapies and precise interventions directed at the cardiac immune microenvironment.