The TXNIP/NLRP3 axis in coronary slow flow: Redox-inflammatory mechanisms and pathological implications

Coronary slow flow (CSF) is a distinct angiographic phenomenon characterized by delayed coronary perfusion in the absence of significant epicardial stenosis, and is associated with recurrent angina, arrhythmias, and adverse cardiovascular outcomes. Increasing evidence implicates oxidative stress and inflammation as central drivers of CSF pathogenesis, with the thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) axis emerging as a key molecular mediator. TXNIP, a redox-sensitive regulator, inhibits thioredoxin activity, promotes reactive oxygen species (ROS) accumulation, and contributes to endothelial dysfunction and mitochondrial impairment. Under oxidative conditions, TXNIP dissociates from thioredoxin and binds to NLRP3, thereby activating the inflammasome, caspase-1, and the maturation of pro-inflammatory cytokines such as IL-1β and IL-18, amplifying vascular injury. This review synthesizes current knowledge on the TXNIP/NLRP3 axis in CSF, highlighting its upstream regulation by pathways such as AMPK, HIF-1α, and mTOR, and its contribution to microvascular inflammation, apoptosis, and atherosclerotic progression. By integrating redox and inflammatory mechanisms, our work introduces a novel pathogenetic framework for CSF that is highly relevant to cardiovascular pathology, and proposes the TXNIP/NLRP3 axis as a potential basis for future diagnostic and therapeutic strategies.