Circulation:NLRP3炎症小体可促进房颤的发生发展

2018-11-17 MedSci MedSci原创

心房颤动(AF)常与炎症反应增强相关。NLRP3(NACHT、 LRR和保护PYD结构域的蛋白质3)炎症体介导免疫细胞的caspase-1激活和白介素-1β释放,但尚不明确其在心肌细胞(CMs)中的具体作用。现研究人员对CM NLRP3炎症小体在AF中的作用进行研究。通过免疫印迹法检测阵发性AF或长期持续性(慢性)AF患者的心房全组织溶解物和CMs的NLRP3炎症小体的激活。为明确NLRP3的CM

房颤动(AF)常与炎症反应增强相关。NLRP3(NACHT、 LRR和保护PYD结构域的蛋白质3)炎症体介导免疫细胞的caspase-1激活和白介素-1β释放,但尚不明确其在心肌细胞(CMs)中的具体作用。现研究人员对CM NLRP3炎症小体在AF中的作用进行研究。

通过免疫印迹法检测阵发性AF或长期持续性(慢性)AF患者的心房全组织溶解物和CMs的NLRP3炎症小体的激活。为明确NLRP3的CM特异性激活是否可有效促进AF,研究人员建立CM特异性表达持续性活化的NLRP3的小鼠模型(CM-KI)。

在阵发性房颤和慢性房颤患者心房中,NLRP3炎性小体活性增强。CM-KI小鼠出现自发性早发型房颤和诱导性房颤,并可被NLRP3炎性小体特异性抑制剂MCC950减弱。此外,CM-KI小鼠还出现异位电活动、肌浆网Ca2+释放异常、心房有效不应期缩短、心房肥大。腺相关病毒亚型-9介导的CM特异性敲除Nlrp3可抑制CM-KI小鼠的AF发展。最后,抑制Nlrp3可阻止CREM转基因小鼠(一种公认的自发性AF的小鼠模型)AF的发生。

本研究揭示了CM NLRP3炎症小体信号的新的病理生理作用,并与AF病理相联系,同时表明抑制NLRP3或可作为治疗AF的新方法。


原始出处:

Chunxia Yao,et al.Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation. 24 Jul 2018. Circulation. 2018;138:2227–2242

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    2018-11-19 yuandd
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    2018-11-19 vera_1207

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