Abstract
Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.
Highlights
Neutrophil extracellular traps (NETs) were initially considered to be one of the first line responses of the immune system against infected bacteria [1], extensive studies have revealed that neutrophil extracellular traps (NETs) formation is associated with the initiation and progression of various noninfectious diseases [2,3]
High-mobility group box 1 (HMGB1), a DNA-binding protein secreted from macrophages and monocytes, which acts as a damage-associated molecular pattern (DAMP) to mediate thrombosis [45], is expressed on activated platelets
NET formation is induced by various stimulants, including exogenous DAMPs, in addition to numerous proinflammatory cytokines
Summary
Neutrophil extracellular traps (NETs) were initially considered to be one of the first line responses of the immune system against infected bacteria [1], extensive studies have revealed that NET formation is associated with the initiation and progression of various noninfectious diseases [2,3]. Accumulating studies have revealed that oxLDL is present in both atherosclerotic lesions and circulation [5] and plays a pivotal role in the progression of CVDs by promoting foam cell formation as well as initiating endothelial inflammatory responses [6]. Neutrophils, in addition to macrophages, are frequently found in vascular lesions; NET formation and the subsequent release of enzymes could presumably potentiate oxLDL production. Insight into the interrelationship between neutrophils and lipoproteins that coexist in the circulation and in vascular lesions under pathological conditions may shed light on a new possibility to understand their roles in vascular diseases. We summarize recent updates on the analysis of NETs and their implications for CVDs. A possible link between NET formation and oxidative modification of lipoproteins has been discussed
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