The Role of Gasdermin-D/Interleukin-1 Nexus in Atrial Arrhythmogenesis

Gasdermin-D/IL-1 Nexus 在房性心律失常发生中的作用

• 批准号: 10779536
• 负责人: Na Li
• 金额: $ 4.76万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10779536
• 关键词: Arrhythmia; Atrial Fibrillation; Cardiac Myocytes; Cell Death; Development; Event; Heart Atrium; Inflammasome; Interleukin-1; Interleukins; Mediating; Membrane; N-terminal; Play; Prevalence; Proteins; Public Health; Role; Work; parent grant; prevent; repaired

PROJECT SUMMARY Atrial fibrillation (AF) is the most frequent arrhythmia. Enhanced activation of ‘NACHT, LRR and PYD domains- containing protein 3’ (NLRP3) inflammasome plays a causal role in promoting proarrhythmic events associated with AF development. Activation of NLRP3 inflammasome produces two major effectors: interleukin (IL)-1b and cleaved (active) N-terminal gasdermin-D (GSDMDNT). Results from parent grant suggest that that GSDMD could promote atrial arrhythmogenesis by previously unrecognized pyroptosis-independent alternative functions in cardiomyocytes and the membrane-repair machinery via ESCRT III may prevent excessive cell death upon inflammasome activation during AF development. In this application, we will elucidate the alternative function of GSDMDNT and the involvement of ESCRT III-mediated membrane repair machinery in cardiomyocytes.

项目摘要 心房颤动（AF）是最常见的心律失常。增强了'NACHT，LRR和PYD结构域的激活 含有蛋白质3'（nlrp3）炎性体在促进促伴有的事件中起因果作用 与自动房屋的开发。 NLRP3炎性体的激活产生两个主要影响：白介素（IL）-1b和 裂解（活跃的）N末端Gasdermin-D（GSDMDNT）。父母赠款的结果表明GSDMD可以 通过以前未被认可的凋亡独立替代功能促进心律失常的发生 通过ESCRT III的心肌细胞和膜修复机械可能会防止过量的细胞死亡 AF开发过程中的炎性体激活。在此应用程序中，我们将阐明 GSDMDNT及其在心肌细胞中ESCRT III介导的膜修复机制的参与。