Neutrophil extracellular traps contributing to atherosclerosis: From pathophysiology to clinical implications

Neutrophil extracellular traps (NETs) are network-like structures of chromatin filaments decorated by histones, granules, and cytoplasmic-derived proteins expelled by activated neutrophils under multiple pathogenic conditions. NETs not only capture pathogens in innate immunity but also respond to sterile inflammatory stimuli in atherosclerosis, such as lipoproteins and inflammatory cytokines. Atherosclerosis is a lipid-driven chronic inflammatory disease characterized by the accumulation and transformation of inflammatory cells, and smooth muscle cells in the intimal space. NETs-derived extracellular components possess toxic and proinflammatory properties leading to cellular dysfunction and tissue damage, which may establish a link among lipid metabolism, inflammatory immunity, and atherosclerosis. In this review, we discuss recent advances regarding the role of NETs engaged in the pathogenesis of atherosclerosis, particularly focusing on the interaction with lipids and inflammasomes, crosstalk with smooth muscle cells and inflammatory cells, and the association with aging. We also evaluate the current knowledge on the potential of NETs as biomarkers and therapeutic targets for atherosclerosis and its related diseases in clinical practice.