Neutrophil Extracellular Traps in Atherosclerosis and Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease of the arterial wall and the leading pathological basis of cardiovascular morbidity and mortality worldwide. Neutrophil extracellular traps (NETs), web-like chromatin structures armed with histones, myeloperoxidase, and serine proteases, have emerged as active participants in vascular inflammation and thrombosis. Under physiological conditions, NETs contribute to host defense and immunothrombosis, but excessive or persistent NET formation drives endothelial injury, plaque progression, and acute coronary events. However, how NETs shift from protective to pathological across the atherosclerotic continuum, and how their individual components cooperate to amplify vascular damage, remain insufficiently understood. This review explores NET homeostasis in the cardiovascular system and the balance between protective and pathological NET release. We then describe the molecular mechanisms of NET formation and the cooperative actions of NET components as an integrated thrombo-inflammatory platform. Next, we discuss stage-specific NET roles throughout atherogenesis, plaque destabilization, and ischemia-reperfusion injury. Finally, we evaluate clinical and translational evidence linking NET biomarkers to cardiovascular outcomes and critically assess precision-targeted NET therapies. This framework highlights NETs as both mechanistic drivers and promising therapeutic targets in atherosclerotic cardiovascular disease.