NF-κB signaling in acute myocardial infarction: pathophysiology, inflammation, and therapeutic implications

Acute myocardial infarction (AMI) triggers a coordinated inflammatory and reparative response that determines infarct healing, ventricular remodeling, and long-term cardiac function. Nuclear factor-kappa B (NF-κB) signaling is a central regulator of this process, but its role is highly context dependent. Early NF-κB activation contributes to danger-signal recognition, immune-cell recruitment, and clearance of necrotic myocardium, whereas sustained activation promotes unresolved inflammation, cardiomyocyte death, fibroblast activation, and adverse ventricular remodeling. This dual function partly explains why experimental studies of NF-κB modulation in AMI have generated heterogeneous and sometimes conflicting results. In this review, we summarize the upstream triggers, temporal dynamics, cell-type-specific actions, and therapeutic implications of NF-κB signaling in AMI. We also discuss the challenges of broad NF-κB inhibition and highlight the need for temporally controlled and cell-selective strategies that preserve reparative inflammation while limiting chronic inflammatory injury and heart failure progression.