刺突介导的 ACE2 下调参与了 SARS-CoV-2 感染的发病机制。
Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection.
机构信息
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518112, China.
Department for Pathology, Shenzhen Third People's Hospital the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
出版信息
J Infect. 2022 Oct;85(4):418-427. doi: 10.1016/j.jinf.2022.06.030. Epub 2022 Jul 3.
The ongoing global pandemic of Coronavirus disease 2019 (COVID-19) poses a serious threat to human health, with patients reportedly suffering from thrombus, vascular injury and coagulation in addition to acute and diffuse lung injury and respiratory diseases. Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA. The decrease of ACE2 and higher level of angiotensin (Ang) II were verified in COVID-19 patients. High dose of Ang II induced pulmonary artery endothelial cell death in vitro, which was also observed in the lung of COVID-19 patients. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.
持续的全球 2019 年冠状病毒病（COVID-19）大流行对人类健康构成严重威胁，据报道患者除急性弥漫性肺损伤和呼吸系统疾病外，还患有血栓、血管损伤和凝血。血管紧张素转换酶 2（ACE2）作为 SARS-CoV-2 进入的受体，也是肾素-血管紧张素系统（RAS）稳态的重要调节剂，在 COVID-19 的发病机制中发挥着不确定的作用。在这里，我们证明 SARS-CoV-2 刺突蛋白激活细胞内信号来降解 ACE2 mRNA。在 COVID-19 患者中验证了 ACE2 的减少和更高水平的血管紧张素（Ang）II。高剂量的 Ang II 在体外诱导肺动脉内皮细胞死亡，在 COVID-19 患者的肺部也观察到了这种现象。我们的发现表明，ACE2 的下调可能将 COVID-19 与 RAS 的失衡联系起来。
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