心血管疾病中的细胞外中性粒细胞陷阱:研究问题与前景

Y. Skirdenko, M. A. Zorkina, D. G. Novikov, A. N. Zolotov, K. Andreev, K.  G. Zinchenko, N. A. Nikolaev
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摘要

心血管疾病的发病机制之一是慢性低强度全身性炎症。2004 年,人们发现了一个以前未知的过程--细胞外中性粒细胞陷阱(NET)的形成--NETosis(中性粒细胞胞外陷阱)。NETs在抗菌免疫中发挥作用,但在某些情况下,NETs会成为病理发展的一个因素。本综述介绍了细胞外嗜中性粒细胞陷阱对心血管系统个别病症(动脉粥样硬化、心房颤动、血栓形成)的影响。作者描述了细胞外中性粒细胞陷阱的形成机制(生命性细胞外中性粒细胞陷阱、自杀性细胞外中性粒细胞陷阱)及其在血栓形成(作为血栓形成的框架、凝血的启动)、内皮功能障碍的发展和心房心肌电异质性中的作用。研究数据表明,动脉粥样硬化、血栓形成和心房颤动与 NETosis 的活动有关。大多数研究证明了实验室模型中存在的相关性,而在实际临床实践中,几乎没有对心血管病患者体内的 NET 进行测定。同时,了解与 NETosis 相关的过程有助于确定心血管疾病治疗的特定标志物和进一步策略。
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Extracellular neutrophil traps in cardiovascular diseases: problems and prospects of research
One of the links in the pathogenesis of cardiovascular diseases is chronic low-intensity systemic inflammation. In 2004, a previously unknown process was discovered — the formation of extracellular neutrophil traps (NETs) — NETosis (n eutrophil extracellular traps). NETs play a role in antimicrobial immunity though in certain cases they become a factor in the development of pathology. This review presents data on the effect of extracellular neutrophil traps on individual pathologies of the cardiovascular system (atherosclerosis, atrial fibrillation, thrombosis). The authors describe the mechanisms of NET formation (vital NETosis, suicidal NETosis) and their role in thrombus formation (as a framework for thrombus formation, initiation of coagulation), in the development of endothelial dysfunction, and electrical heterogeneity of the atrial myocardium. Data are presented indicating the connection between atherosclerosis, thrombosis, and atrial fibrillation with the activity of NETosis. Most studies demonstrate existing correlations on laboratory models, while the determination of NETs in patients with cardiovascular pathology in real clinical practice is almost absent. At the same time, understanding the processes associated with NETosis can help to identify specific markers and further strategies for the therapy of cardiovascular diseases.
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