Targeting the NLRP3 inflammasome in cardiovascular diseases.
Targeting the NLRP3 inflammasome in cardiovascular diseases.
复制标题
靶向NLRP3炎性体在心血管疾病中的作用。
DOI：
10.1016/j.pharmthera.2021.108053
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发表时间：
2022-08
影响因子：
13.5
通讯作者：
Abbate, Antonio
中科院分区：
文献类型：
--
作者：
Toldo, Stefano;Mezzaroma, Eleonora;Buckley, Leo F.;Potere, Nicola;Di Nisio, Marcello;Biondi-Zoccai, Giuseppe;Van Tassell, Benjamin W.;Abbate, Antonio
关键词：
NACHT、富含亮氨酸重复序列（LRR）和含有pyrin结构域（PYD）的蛋白3（NLRP 3）炎性体是在先天免疫中起主要作用的细胞内传感蛋白复合物。组织损伤后，NLRP 3炎性体的激活导致细胞因子产生，主要是白介素（IL）-1β和IL-18，最终导致炎性细胞死亡-细胞凋亡。虽然平衡的炎症反应有利于损伤消退和组织愈合，但过度的NLRP 3激活会导致有害影响。NLRP 3炎性小体的关键参与已经在广泛的心血管疾病（CVD）中报道。已经开发了几种选择性靶向NLRP 3炎性体系统的药理学试剂，并在动物和早期人类研究中进行了测试，总体结果令人鼓舞。虽然NLRP 3抑制剂处于临床开发阶段，但多项随机试验已证明IL-1阻断剂在动脉粥样硬化血栓形成、心力衰竭和复发性心包炎中的安全性和有效性。此外，非选择性NLRP 3抑制剂秋水仙碱最近已被证明可显著减少慢性冠状动脉疾病患者的心血管事件。本文综述了NLRP 3的组装和激活机制，并讨论了NLRP 3炎性小体在心血管疾病中的致病作用，并对目前和未来针对NLRP 3炎性小体的治疗方法进行了综述。
The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that plays a major role in innate immunity. Following tissue injury, activation of the NLRP3 inflammasome results in cytokine production, primarily interleukin(IL)-1β and IL-18, and, eventually, inflammatory cell death – pyroptosis. While a balanced inflammatory response favors damage resolution and tissue healing, excessive NLRP3 activation causes detrimental effects. A key involvement of the NLRP3 inflammasome has been reported across a wide range of cardiovascular diseases (CVDs). Several pharmacological agents selectively targeting the NLRP3 inflammasome system have been developed and tested in animals and early phase human studies with overall promising results. While the NLRP3 inhibitors are in clinical development, multiple randomized trials have demonstrated the safety and efficacy of IL-1 blockade in atherothrombosis, heart failure and recurrent pericarditis. Furthermore, the non-selective NLRP3 inhibitor colchicine has been recently shown to significantly reduce cardiovascular events in patients with chronic coronary disease. In this review, we will outline the mechanisms driving NLRP3 assembly and activation, and discuss the pathogenetic role of the NLRP3 inflammasome in CVDs, providing an overview of the current and future therapeutic approaches targeting the NLRP3 inflammasome.
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影响因子：
1.6
作者：
Quader M;Mezzaroma E;Wickramaratne N;Toldo S
通讯作者：
Toldo S
影响因子：
6
作者：
Butts B;Gary RA;Dunbar SB;Butler J
通讯作者：
Butler J
DOI：
10.3390/molecules26123534
发表时间：
2021-06-09
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Aliaga J;Bonaventura A;Mezzaroma E;Dhakal Y;Mauro AG;Abbate A;Toldo S
通讯作者：
Toldo S
影响因子：
9.3
作者：
Cai J;Lu S;Yao Z;Deng YP;Zhang LD;Yu JW;Ren GF;Shen FM;Jiang GJ
通讯作者：
Jiang GJ
影响因子：
3.8
作者：
Ballak DB;Stienstra R;Tack CJ;Dinarello CA;van Diepen JA
通讯作者：
van Diepen JA