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以IGF1为媒介的中细胞-内皮细胞过渡作为动性大动脉病的潜在调节目标

Binglin Li¹, Mi Zhou², Jianghong Guo³

¹Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, NO.241 Huaihai West Road, Shanghai, China.

|November 4, 2025

概括

大动脉间细胞 (VICs) 在性大动脉病 (CAVD) 中可以转化为内皮细胞. 这种由IGF1介导的介细胞内皮过渡 (MEndT) 途径为CAVD提供了一个新的治疗点.

科学领域:

心血管生物学心血管生物学
细胞生物学细胞生物学
再生医学是一种再生医学.

背景情况:

大动脉间歇细胞 (VICs) 是一种具有已知的分化潜力的塑性介质细胞群.
在患病的大动脉中观察到的内皮细胞的起源尚不清楚,因为正常的门是无血管的.
以前的研究没有证实VICs能够分化为内皮细胞的能力.

研究的目的:

调查VICs在内皮细胞分化中的潜力.
为了确定分子机制驱动这种过渡在形大动脉膜疾病 (CAVD) 的背景下.
探索针对这一过程的治疗策略.

主要方法:

人类CAVD组织的免疫光分析.
主要VIC和膜内皮细胞 (VEC) 的隔离和功能测定.
转录组测序,西斑,qPCR和免疫光学以阐明分子途径.
一个CAVD鼠标模型的构建和分析.
使用公共单细胞测序数据进行验证.

主要成果:

在骨质刺激下,VICs表现出内皮标记物的表达增加,并获得了内皮功能.
鉴定出IGF1-PI3K-AKT-HIF通路是介导介质细胞内皮过渡 (MEndT) 的.
在小鼠中,IGF1的使用促进了内皮细胞的产生,并减轻了CAVD的进展,而IGF1R抑制剂则逆转了这种效应.

结论:

在特定条件下,VICs可以经历内皮过渡,这一过程称为MEndT.
在CAVD期间,MEndT发生在主动脉中,涉及IGF1信号通路.
MEndT代表了CAVD的一个潜在的治疗点.

关键词:

动脉的疾病动脉疾病 IGF1 IGF1 的一个例子.介质细胞-内皮细胞过渡

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