固体细胞的SARS-CoV-2感染,依赖于流动诱导的ACE2表达,在血管化的微生理系统中驱动超细胞因子症
Christopher J Hatch1, Sebastian D Piombo2, Jennifer S Fang3
1Department of Biomedical Engineering, University of California, Irvine, CA, United States.
Frontiers in cardiovascular medicine
|April 5, 2024
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染引发血管炎症和凝血病. 一个3D微生理系统揭示了流动诱导的ACE2表达增加了SARS-CoV-2的易感性,并驱动了超细胞因子症.
科学领域:
- 血管生物学 血管生物学
- 病毒学 病毒学
- 传染病的发病因子传染病的发病因子
背景情况:
- 由SARS-CoV-2引起的COVID-19导致严重的细胞高血和内皮损伤.
- 疫苗接种减少了住院治疗,但在突破性感染中仍然存在高细胞动血症.
- 有需要的疾病模型,准确地模仿SARS-CoV-2-诱导的超细胞因子症.
研究的目的:
- 通过使用3D微生理系统 (MPS) 调查血管系统在SARS-CoV-2-诱导的高细胞因子症中的作用.
- 在血管化微器官 (VMO) 平台中模拟SARS-CoV-2感染.
- 在生理流条件下,评估病毒感染对内皮细胞 (ECs) 的影响.
主要方法:
- 在细胞外基质中使用了VMO MPS,其中包括人类初级EC和细胞外基质细胞.
- 使用表达GFP的非复制性伪型病毒来可视化病毒进入EC.
- 分析了ACE2,TMPRSS2和AGTR1的表达,并评估了病毒对ACE2表达,血管炎症和形态的影响.
主要成果:
- VMO平台启用了对COVID-19血管感染的研究.
- 随着剪切压力,ACE2表达显著增加,增强了伪型SARS-CoV-2感染的易感性.
- 受感染的EC释放出促炎性细胞因子 (例如IL-6) 和凝血因子,激活下游EC并放大炎症和凝血病.
结论:
- 血管系在COVID-19病变发生过程中发挥着至关重要的作用.
- 流动诱导的ACE2表达在启动炎症反应方面具有重要意义.
- VMO MPS是研究SARS-CoV-2感染动态和评估治疗方法的宝贵工具.
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