在COVID-19患者中,血小板前性eNOS阴性血小板的水平升高
Amir Asgari1, Aleksandra Franczak2, Alex Herchen3
1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
严重的COVID-19与更多缺乏内皮氧化合成酶 (eNOS) 的血小板有关,增加了血栓形成的风险. 这种转变是由炎症驱动的,影响大核细胞eNOS表达和血小板功能.
科学领域:
- 血液学 血液学 血液学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 严重的COVID-19与富有血小板的微血管血栓有关.
- 内生氧化 (NO) 信号,特别是通过内皮氧化合成酶 (eNOS),调节血栓形成.
- 细胞因子可以反调节eNOS表达,可能会在COVID-19期间改变巨核细胞和血小板eNOS水平.
研究的目的:
- 为了确定COVID-19患者是否表现出eNOS阴性血小板的百分比增加.
- 调查促炎性细胞因子是否影响巨核细胞eNOS表达,导致血小板亚群的改变.
- 为了将eNOS阳性和eNOS阴性血小板的变化与COVID-19的严重程度和血小板激活相关联.
主要方法:
- 从住院的COVID-19患者和对照人群中分离了血小板,用于对eNOS表达的流动细胞计分析.
- 血炎性细胞因子 (TNF-α,IL-6,IL-1β) 通过ELISA量化.
- 巨核细胞 (eNOS-GFP转基因小鼠,Meg-01细胞系) 用于模拟基于eNOS的血小板亚群形成,以应对细胞因子.
主要成果:
- 与对照组相比,COVID-19患者的eNOS阴性血小板显著增加,eNOS阳性血小板减少.
- 增加的eNOS阴性与eNOS阳性血小板比率与疾病严重程度 (ICU入院) 和增加的血小板激活 (CD62P表达) 相相关.
- 在COVID-19患者中观察到TNF-α,IL-6和IL-1β的血水平升高;这些细胞因子在体外促进了eNOS阴性巨核细胞和血小板状颗粒的形成.
结论:
- COVID-19患者表现出更高比例的eNOS阴性血小板,与血栓形成风险增加有关.
- 这种血小板表型可能是炎症反应的结果,这些炎症反应减少了巨核细胞中eNOS的表达.
- 这些发现突出了一个机制,通过该机制,COVID-19相关的炎症有助于形成血栓形成状态.
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