Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.
St. John Paul II Hospital, Kraków, Poland.
Kardiol Pol. 2023;81(12):1205-1216. doi: 10.33963/v.kp.98520.
Neutrophil extracellular traps (NETs), which are net-like structures composed of DNA, histones, and antimicrobial proteins, in particular myeloperoxidase (MPO) and elastase, have been demonstrated in bacterial, viral, protozoal, and fungal infections as a potent innate immunity mechanism of pathogen elimination associated with enhanced inflammation. Growing evidence indicates the contribution of NETs formation (NETosis), driven by protein-arginine deiminase type 4, to thrombosis, ischemia, and atherosclerosis. NETs are considered new players involved in the development and progression of cardiovascular diseases (CVDs), including coronary artery disease (CAD) and its acute manifestations in particular acute myocardial infarction (MI), peripheral artery disease (PAD) along with ischemic stroke, heart failure, aortic stenosis, and atrial fibrillation (AF). Formation of NETs and elevated levels of their circulating markers, e.g. citrullinated histone 3 and MPO-DNA complexes, have been observed in chronic and acute manifestations of CVD. NETs accumulation was associated with plaque rupture, infarct size, and impaired myocardial function. NETs have been identified within human stenotic aortic valves, like in atherosclerotic plaques and arterial thrombi. Moreover, circulating NETs markers in association with prothrombotic markers, including fibrin clot properties, predicted adverse clinical events in AF. Several NETs inhibitors, including recombinant human DNase, an enzyme degrading NETs, reactive oxygen species scavengers, together with antithrombotic and antiplatelet drugs, have been shown to reduce uncontrolled NETosis. This review summarizes the current evidence on the role of NETosis in CVDs, its significance as a risk factor for clinical outcomes, and finally, the potential of NETs as a target for future therapeutic interventions.
中性粒细胞胞外诱捕网（NETs）是一种由 DNA、组蛋白和抗菌蛋白（尤其是髓过氧化物酶（MPO）和弹性蛋白酶）组成的网状结构，已在细菌、病毒、原生动物和真菌感染中被证实为一种有效的病原体消除的先天免疫机制，与增强的炎症有关。越来越多的证据表明，由蛋白精氨酸脱亚氨酶 4 驱动的 NETs 形成（NETosis）有助于血栓形成、缺血和动脉粥样硬化。NETs 被认为是参与心血管疾病（CVDs）发展和进展的新因素，包括冠状动脉疾病（CAD）及其急性表现，特别是急性心肌梗死（MI）、外周动脉疾病（PAD）以及缺血性中风、心力衰竭、主动脉瓣狭窄和心房颤动（AF）。在 CVD 的慢性和急性表现中观察到 NETs 的形成和其循环标志物（例如，瓜氨酸化组蛋白 3 和 MPO-DNA 复合物）水平升高。NETs 的积累与斑块破裂、梗死面积和心肌功能受损有关。已经在人类狭窄的主动脉瓣中鉴定出 NETs，就像在动脉粥样硬化斑块和动脉血栓中一样。此外，与促血栓形成标志物（包括纤维蛋白凝块特性）相关的循环 NETs 标志物可预测 AF 中的不良临床事件。几种 NETs 抑制剂，包括降解 NETs 的重组人 DNA 酶、活性氧物质清除剂，以及抗血栓和抗血小板药物，已被证明可减少不受控制的 NETosis。本综述总结了 NETosis 在 CVDs 中的作用的现有证据，其作为临床结果的危险因素的意义，以及最后，NETs 作为未来治疗干预靶点的潜力。
