From atherosclerosis to reperfusion injury: a comprehensive review of neutrophil extracellular traps across the spectrum of coronary heart disease

Neutrophil extracellular traps (NETs) have emerged as critical mediators in the pathogenesis of coronary heart disease (CHD), linking innate immunity, thrombosis, and vascular inflammation. This review offers a comprehensive overview of NETs across the spectrum of CHD, ranging from chronic atherosclerotic plaque development to acute coronary syndrome, myocardial infarction, and ischemia-reperfusion injury. We first summarize the molecular mechanisms underlying NET formation, their regulation, and their dual roles in immune defense and vascular damage. Next, we discuss evidence highlighting the contribution of NETs to plaque initiation, progression, and destabilization, as well as their role in thrombosis following plaque rupture and their impact on myocardial injury and microvascular obstruction during reperfusion. Our review also integrates clinical and translational insights, including circulating NETs as potential biomarkers for disease activity and prognosis, and emerging therapeutic strategies aimed at either inhibiting NET formation or enhancing NET clearance. By positioning NETs within the continuum of coronary pathology, this review highlights their central role in thromboinflammatory cascades and identifies opportunities for innovative interventions to mitigate both acute and chronic cardiac injury.