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帕诺亡是胸前大动脉动脉瘤或剖析中突出的细胞死亡特征

Xu Xu¹, Yaxin Zhu¹, Yuting Niu²

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

Experimental cell research

|September 14, 2024

概括

编程细胞死亡的PANoptosis与胸前大动脉动脉瘤和解剖 (TAAD) 有关. Z-DNA结合蛋白1 (ZBP1) 的激活驱动TAAD中的PANoptosis,提供潜在的治疗点.

科学领域:

心血管生物学心血管生物学
细胞死亡机制细胞死亡机制
分子病理学分子病理学

背景情况:

胸前动脉动脉瘤和解剖 (TAAD) 是一种严重的血管疾病,原因不明.
编程细胞死亡 (PCD) 途径越来越多地被认为是它们在疾病发病过程中的作用.
泛,一种新定义的PCD,涉及热,光和死,已成为一个重要的生物过程.

研究的目的:

调查PANoptosis在TAAD病变发生中的作用.
探索Z-DNA结合蛋白1 (ZBP1) 在TAAD相关的PANoptosis中的参与.
根据PANoptosis机制,确定TAAD的潜在治疗点.

主要方法:

使用了一种由β-aminopropionitrile (BAPN) 和Angiotensin II (Ang II) 诱导的TAAD小鼠模型.
分析了小鼠大动脉组织中ZBP1和PANoptosis相关基因的表达.
在Ang II刺激下检查人类大动脉血管光滑肌细胞 (HASMCs),以评估PANoptosis的特征.
研究了人类TAAD患者的大动脉组织中ZBP1介导的PANoptosis.

主要成果:

在TAAD小鼠模型中观察到ZBP1和PANoptosis相关基因的升级表达.
在HASMCs中的Ang II刺激导致ZBP1表达增加,生物活性Gasdermin D (GSDMD) 片段生成,Caspase 3裂变和MLKL酸化,表明PANoptosis激活.
在人类TAAD患者的大动脉组织中证实了ZBP1介导的PANoptosis.

结论:

在TAAD的发病过程中,PANoptosis扮演着重要的角色.
在TAAD中,ZBP1是PANoptosis的关键媒介.
ZBP1和其他与PANoptosis相关的基因代表了TAAD治疗的有前途的治疗标.

关键词:

ангиотензин II 的使用.人类大动脉血管平滑肌肉细胞这就是PANoptosis.胸前大动脉动脉瘤和剖析在 ZBP1 中,ZBP1 是

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