From marrow memory to adverse ventricular remodeling: trained immunity after myocardial infarction

Abstract

Myocardial infarction [MI] triggers a sterile inflammatory response that is essential for necrotic-tissue clearance and scar formation and should normally subside as repair progresses. In a subset of patients, however, persistent myeloid activation accompanies progressive fibrosis, ventricular dilatation, and adverse remodeling long after the acute insult. Trained immunity may help explain this temporal mismatch by allowing myocardial injury to leave a durable functional bias in innate immune cells or their hematopoietic progenitors. Damage-associated molecular patterns, inflammatory cytokines, and sympathetic signals released after MI may reprogram bone-marrow hematopoiesis through metabolic and epigenetic mechanisms. Bone-marrow-derived cells can enter the circulation and injured myocardium directly; the spleen may provide an additional reservoir, hematopoietic niche, and amplification or deployment compartment rather than an obligatory intermediate. Resident and recruited cardiac macrophages then interpret this systemic input within the heart, where macrophage-fibroblast-extracellular matrix interactions influence scar composition, remote-zone fibrosis, ventricular geometry, and progression toward heart failure. This review follows a heart-hematopoietic-heart network and distinguishes direct MI-trained-immunity evidence from MI-specific bridging evidence, adjacent trained-immunity models, and downstream remodeling evidence. Individual components are supported to different degrees, but causal continuity from MI-induced hematopoietic memory to adverse ventricular remodeling has not yet been demonstrated. Defining where durable memory is established, how myeloid output reaches the heart, and when it becomes maladaptive may support phase-specific interventions that preserve early repair while limiting later inflammation and fibrosis.