通过ACE2,SARS-CoV-2尖端蛋白诱导内皮炎症,独立于病毒复制
Augusto C Montezano1,2, Livia L Camargo3, Sheon Mary4
1Research Institute of the McGill University Health Centre (RI-MUHC), Site Glen-Block E-Office: E01.3362, 1001, Boul. Decarie, Montreal, QC, H4A3J1, Canada. augusto.montezano@muhc.mcgill.ca.
Scientific reports
|August 28, 2023
概括
SARS-CoV-2尖端蛋白通过ACE2触发内皮细胞的炎症,导致COVID-19内皮炎. 这独立于ACE2发生.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- COVID-19是一种由SARS-CoV-2引起的呼吸系统疾病,涉及炎症和内皮炎.
- 驱动这些炎症过程的确切机制尚不清楚.
- ангиотензин转化酶2 (ACE2),SARS-CoV-2尖端蛋白受体,是一个潜在的关键参与者.
研究的目的:
- 为了调查SARS-CoV-2尖端蛋白与ACE2结合是否诱导内皮炎症.
- 确定ACE2在调解这种炎症反应中的特定作用.
主要方法:
- 人体内皮细胞暴露于SARS-CoV-2尖端蛋白 (rS1p).
- 使用药理学剂和siRNA.RNA调节了ACE2功能.
- 评估了促炎信号和媒介,以及微粒形成.
- 细胞也暴露于SARS-CoV-2病毒.
主要成果:
- rS1p暴露增加了IL-6,MCP-1,ICAM-1和PAI-1的产生,通过ACE2激活NFkB.
- rS1p诱导的微粒形成,表明内皮损伤.
- 确定了参与炎症和RNA生物学的ACE2相互作用蛋白.
- 无论是ACE2表达还是酶活性都没有被rS1p改变;没有观察到病毒复制.
结论:
- 通过ACE2,SARS-CoV-2尖端蛋白会诱导内皮炎症和损伤.
- 这个过程独立于ACE2酶活性和病毒复制.
- 在COVID-19相关的内皮质炎中,ACE2起着新的作用.
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