Neutrophil extracellular traps in the pathogenesis of pre-eclampsia: immunoinflammatory and thrombotic mechanisms

Abstract

Pre-eclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. Current understanding extends beyond the exclusively angiogenic concept and regards the disease as an immunoinflammatory and thrombotic syndrome arising from the interaction of placental ischemia, oxidative stress, endothelial dysfunction, and activation of the coagulation cascade. In recent years, particular attention has been given to the role of neutrophil extracellular traps (NETs), which are innate immune structures with pronounced proinflammatory and prothrombotic properties. NETs form a threedimensional scaffold for platelet aggregation and fibrin deposition, promote tissue factor expression, exacerbate oxidative endothelial injury, and sustain the thromboinflammatory cascade. Increased NET formation has been revealed in the placenta and maternal circulation in PE, suggesting their role as a mechanistic link between inflammation, coagulation, and vascular dysfunction. This review systematizes current data on the mechanisms of NET formation, their biological effects, and potential therapeutic targets in PE. It also discusses strategies for modulating NETosis, including targeting NET components and anticoagulant approaches. Despite compelling experimental evidence, the clinical significance of NETs in PE requires further investigation. Key words: pre-eclampsia, neutrophil extracellular traps, thromboinflammation, endothelial dysfunction, NETosis, oxidative stress