NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?
NLRP3-Induced NETosis: A Potential Therapeutic Target for Ischemic Thrombotic Diseases?
复制标题
nlrp3诱导的NETosis：缺血性血栓性疾病的潜在治疗靶点？
作者：
缺血性血栓性疾病的特征是在动脉或静脉内形成阻塞性血凝块，是一种与危及生命的事件相关的疾病，如中风、心肌梗死、深静脉血栓形成和肺栓塞。传统的治疗策略依赖于使用抗凝剂的治疗，不幸的是，抗凝剂具有出血并发症的固有风险。这些抗凝剂主要靶向凝血因子，通常忽略上游事件，包括中性粒细胞胞外陷阱（NET）的释放。中性粒细胞是先天免疫系统的组成部分，传统上已知其通过NET形成在对抗病原体中的作用。新出现的证据表明，NET通过促进血小板活化、增加凝血酶生成和为凝块形成提供支架来促进血栓形成。此外，NET组分增强凝块稳定性和抗纤维蛋白溶解性。临床和临床前研究已经强调了NET在血栓性并发症的发病机制中的机制参与，因为从患者和实验模型获得的凝块一致地表现出NET的存在。鉴于这些见解，NET或NET形成的抑制正在成为缺血性血栓性疾病的有希望的治疗方法。最近的研究还暗示了核苷酸结合寡聚化结构域（NOD）样受体家族含吡林结构域3（NLRP 3）炎性体作为NETosis和血栓形成的介体的作用，表明NLRP 3抑制也可能具有减轻血栓形成事件的潜力。因此，未来的临床前和临床研究，旨在确定和验证NLRP 3抑制作为一种新的治疗干预血栓性疾病是必要的。
Ischemic thrombotic disease, characterized by the formation of obstructive blood clots within arteries or veins, is a condition associated with life-threatening events, such as stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism. The conventional therapeutic strategy relies on treatments with anticoagulants that unfortunately pose an inherent risk of bleeding complications. These anticoagulants primarily target clotting factors, often overlooking upstream events, including the release of neutrophil extracellular traps (NETs). Neutrophils are integral components of the innate immune system, traditionally known for their role in combating pathogens through NET formation. Emerging evidence has now revealed that NETs contribute to a prothrombotic milieu by promoting platelet activation, increasing thrombin generation, and providing a scaffold for clot formation. Additionally, NET components enhance clot stability and resistance to fibrinolysis. Clinical and preclinical studies have underscored the mechanistic involvement of NETs in the pathogenesis of thrombotic complications, since the clots obtained from patients and experimental models consistently exhibit the presence of NETs. Given these insights, the inhibition of NETs or NET formation is emerging as a promising therapeutic approach for ischemic thrombotic diseases. Recent investigations also implicate a role for the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome as a mediator of NETosis and thrombosis, suggesting that NLRP3 inhibition may also hold potential for mitigating thrombotic events. Therefore, future preclinical and clinical studies aimed at identifying and validating NLRP3 inhibition as a novel therapeutic intervention for thrombotic disorders are imperative.
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影响因子：
--
作者：
Martirosyan A;Petrek M;Navratilova Z;Blbulyan A;Boyajyan A;Manukyan G
通讯作者：
Manukyan G
影响因子：
4.6
作者：
Nordeng J;Schandiz H;Solheim S;Åkra S;Hoffman P;Roald B;Bendz B;Arnesen H;Helseth R;Seljeflot I
通讯作者：
Seljeflot I
影响因子：
7.3
作者：
de Zoete MR;Flavell RA
通讯作者：
Flavell RA
DOI：
10.1161/atvbaha.113.301627
发表时间：
2013-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Borissoff JI;Joosen IA;Versteylen MO;Brill A;Fuchs TA;Savchenko AS;Gallant M;Martinod K;Ten Cate H;Hofstra L;Crijns HJ;Wagner DD;Kietselaer BLJH
通讯作者：
Kietselaer BLJH
Netosis作为类风湿关节炎中自身抗原的来源。
影响因子：
7.3
作者：
Corsiero E;Pratesi F;Prediletto E;Bombardieri M;Migliorini P
通讯作者：
Migliorini P