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动脉瘤受限于通过PDGFRb-PI3K轴的CD34⁺细胞形成的纤维结

Hong Wu¹, Xiaoping Yang², Ting Chen¹

¹Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|December 28, 2024

概括

CD34+细胞对于腹腔大动脉动脉瘤 (AAA) 的发展至关重要. 非骨髓CD34+细胞转基因分化为肌纤维细胞,有助于纤维化领和AAA进展. 针对这种途径可能为AAA提供新的治疗策略.

科学领域:

心血管生物学心血管生物学
干细胞研究干细胞研究
大动脉动脉瘤病变的发病因子

背景情况:

大动脉动脉瘤涉及连接组织失衡.
CD34+细胞具有干细胞和原始细胞的特性.
在腹腔大动脉动脉瘤 (AAA) 中CD34+细胞的作用尚不清楚.

研究的目的:

为了研究CD34+细胞在AAA病变发生中的作用.
在AAA中确定CD34+细胞的细胞起源和功能.
阐明调节CD34+细胞参与AAA的分子机制.

主要方法:

在人类和小鼠大动脉中对CD34表达的分析.
使用Cd34-CreER^T2;Rosa26-tdTomato;(Apoe^-/-) 模型进行血统追踪.
骨髓移植和单细胞测序.
选择性消耗CD34+细胞和肌纤维细胞.
对PDGF-PDGFRb-PI3K信号通路的研究.

主要成果:

在动脉瘤大动脉中,CD34表达的下调.
非骨髓的CD34+细胞转基因化为Periostin+肌纤维细胞,在AAA中形成纤维化领.
CD34+细胞或肌纤维细胞的枯竭会加剧AAA的进展和死亡率.
PDGF-PDGFRb-PI3K轴对于CD34+细胞的肌纤维细胞生成至关重要.

结论:

CD34+细胞,特别是非骨髓衍生细胞,在AAA病变发生过程中发挥着关键作用.
CD34+细胞转基因分化为Periostin+肌纤维细胞是纤维化结形成的一个关键机制.
PDGF-PDGFRb-PI3K通路代表了AAA治疗的潜在治疗标.

关键词:

在CD34+细胞中.这是PDGFRbb.动脉动脉瘤的发生纤维细胞的细胞.遗传细胞谱系的追踪遗传细胞谱系的追踪

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