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.

项目概要 心房颤动（AF）是最常见的心律失常。增强“NAHT”、“LRR”和“PYD”域的激活- 含有蛋白 3' (NLRP3) 的炎症小体在促进相关致心律失常事件中发挥因果作用 随着 AF 的发展。 NLRP3 炎症小体的激活产生两个主要效应子：白细胞介素 (IL)-1b 和 裂解（活性）N 末端gasdermin-D (GSDMDNT)。家长资助的结果表明 GSDMD 可以 通过以前未被识别的细胞焦亡独立的替代功能促进房性心律失常的发生 心肌细胞和通过 ESCRT III 的膜修复机制可以防止细胞过度死亡 AF 发展过程中炎症小体的激活。在此应用中，我们将阐明以下替代函数 GSDMDNT 和 ESCRT III 介导的心肌细胞膜修复机制的参与。