升高的剪切应力调节异质细胞亚群,诱导血管重塑
Katharina S Fischer1,2,3, Dominic Henn1,2,4, Eric T Zhao5
1Department of Surgery, University of Arizona, Tucson, Arizona, USA.
Tissue engineering. Part A
|May 16, 2024
概括
升高的剪切应力 (ESS) 导致静脉中细胞反应均,促进血管重塑. 了解这些分子变化是防止动脉静脉囊衰竭的关键.
科学领域:
- 血管生物学 血管生物学
- 血液动力学 血液动力学
- 单细胞基因组学 单细胞基因组学
背景情况:
- 由于动脉化,静脉中的剪切应力 (ESS) 升高,导致血管重塑和动脉静脉 (AV) 片失败.
- 在ESS诱导的重塑背后的分子机制缺乏单细胞分辨率.
研究的目的:
- 使用单细胞分辨率,在ESS下参与血管重塑的细胞亚群和分子机制的全面表征.
- 为了研究ESS与没有升高的剪切应力 (NSS) 对AV鱼模型中细胞异质性和基因表达的影响.
主要方法:
- 采用了体内大鼠模型,在白血管中创建了AV循环.
- 采用单细胞RNA测序和组织病理学来分析细胞反应.
- 在ESS条件下的静脉改造与控制 (NSS) 条件进行比较.
主要成果:
- 在内皮细胞 (ECs) 中,ESS诱导了转录的同质性,促进了血管生成和升调Klf2 (抑制内皮细胞到介质酶的过渡).
- 国家安全系统导致了EC异质性,上调了抗扩散基因 (Cav1,Cst3,Btg1).
- 在巨细胞中,ESS促进了同质的,亲炎性,亲血管性髓状细胞表型,而NSS髓状细胞表达了抗炎性Mrc1.1.
结论:
- ESS激活了统一的基因表达特征,用于血液动力学适应.
- 针对已识别的细胞亚群,可能为预防过度静脉重塑,内增生和AV囊衰竭提供新的疗法.
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