ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN ATHEROSCLEROTIC PLAQUE INSTABILITY

Abstract

Atherosclerosis remains a leading cause of morbidity and mortality worldwide, driven by a complex interplay of chronic inflammation, endothelial dysfunction, and oxidative stress. This study investigated the molecular and cellular mechanisms underlying atherosclerosis progression with a particular focus on inflammatory cytokines, oxidative biomarkers, endothelial injury, and neutrophil extracellular traps (NETs). A total of 100 participants, including clinically diagnosed atherosclerosis patients and healthy controls, were assessed through biochemical, immunological, and molecular analyses. Results demonstrated significantly elevated levels of TNF-α, IL-6, and IL-1β in the atherosclerosis group, indicating a heightened pro-inflammatory state. Oxidative stress markers showed increased malondialdehyde (MDA) and reduced antioxidant enzymes such as superoxide dismutase (SOD) and glutathione (GSH), confirming oxidative imbalance. Endothelial dysfunction was evident from upregulated vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), along with decreased nitric oxide levels. Importantly, NETs biomarkers—citrullinated histone H3 (CitH3) and myeloperoxidase-DNA complexes—were significantly higher in patients, highlighting the role of NETosis in plaque instability. Correlation analysis revealed strong associations between NETs and pro-inflammatory cytokines (r > 0.69, p < 0.001), and logistic regression identified CitH3, TNF-α, MDA, and VCAM-1 as independent predictors of plaque vulnerability. These findings provide a multidimensional view of atherosclerosis pathogenesis, integrating immune, oxidative, and vascular markers. The results underscore the potential of NETs and inflammatory mediators as novel biomarkers and therapeutic targets for early intervention. This study advances our understanding of the disease’s mechanistic underpinnings and supports the need for targeted strategies beyond lipid-lowering therapies, focusing instead on inflammation and endothelial repair to prevent plaque rupture and associated cardiovascular events.