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Updated: May 16, 2025

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人体NAP1L1 p.D349E通过cGAS-STING-IFN信号传递促进心脏缩

Cheng Lv¹, Xiayidan Alimu¹, Xiao Xiao¹

¹State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Nature communications

|April 1, 2025

概括

在NAP1L1基因 (p.D349E) 中的体变异通过激活免疫反应,有助于高伤心肌病 (HCM). 这一发现为基因难以捉摸的零星HCM病例提供了新的见解.

科学领域:

心血管医学心血管医学
遗传学是一个遗传学.
免疫学免疫学免疫学

背景情况:

增高性心肌病变 (HCM) 是一种主要的遗传性心脏病,经常与sarcomere基因突变有关.
偶发性HCM病例的很大一部分缺乏确定的遗传原因,这表明存在未知的促成因素.

研究的目的:

调查体变异在零星,基因难以捉摸的HCM遗传基础中的角色.
阐明分子机制,通过确定体质变体有助于心脏缩.

主要方法:

使用下一代测序来识别偶发性HCM患者心肌细胞中复发性体质变异.
进行了体内和体外功能测试,以验证NAP1L1 p.D349E变种的致病性.

主要成果:

身体变异NAP1L1 p.D349E经常在零星HCM患者的心肌细胞中被发现,缺乏其他遗传解释.
证明NAP1L1 p.D349E会破坏核细胞形成的稳定,导致细胞质DNA泄漏.
这种DNA泄漏激活了cGAS-STING天生的免疫通路,诱导炎症并促进心脏缩.

结论:

阴性变异,特别是NAP1L1 p.D349E,代表了一种新的机制,在零星情况下导致过度缩性心肌病变.
这些发现突显了体质突变在理解基因难以捉摸的HCM病因学的重要性.
准先天免疫反应途径可能为HCM管理提供新的治疗策略.

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