在动脉样硬化斑块中,切割应力与动脉保护性KLK10脱
Ziqi Zhou1, Suze-Anne Korteland2, Blanca Tardajos-Ayllon3
1Department of Infection, Immunity and Cardiovascular Disease, INSIGNEO Institute, and the Bateson Centre, University of Sheffield, Sheffield, UK.
Atherosclerosis
|October 16, 2024
概括
生理剪切应激通常会保护血管,但这种作用在动脉样硬化时会消失. 患病的动脉对剪切压力的反应减少,导致内皮细胞 (EC) 炎症和亡.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞生物学 内皮细胞生物学
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 生理剪切应激通过诱导内皮细胞 (EC) 中的保护分子来维持血管平衡.
- 矛盾的是,剪切压力可以促进心血管风险因素的个体的动脉样硬化.
- 患病的动脉可能对剪切应力的保护作用的反应能力降低.
研究的目的:
- 调查病动脉对生理剪切压力的反应能力降低的假设.
- 为了比较健康和动脉样硬化条件下的EC暴露于剪切应力的转录组.
主要方法:
- 利用3D光片成像和计算流体动力学来识别NOS3作为剪切应力标记.
- 从健康和动脉样硬化小鼠 (Apoe-/-) 的EC上进行单细胞RNA测序.
- 在不同疾病状态中比较No3high (shear-exposed) EC的转录组.
主要成果:
- 健康动脉中的高EC显示出保护性标记物,而患病动脉中的保护性标记物则为炎症和亡基因表达增强.
- 确定了8个EC子集,这些子集在健康动脉和患病动脉之间有比例的差异.
- 发现KLK10是一种动脉保护因子,富含健康的高EC值,但在严重病变的动脉中降低.
结论:
- 生理剪切应力在动脉样硬化斑块内失去其动脉样保护功能.
- 这种脱凸显了剪切应力,内皮功能障碍和动脉样硬化进展之间的复杂相互作用.
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