Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection. Issue 4 (October 2022) - Gao, Xiang
Highlights: The expression of ACE2 in infected cells was down-regulated during SARS-CoV-2 infection. SARS-CoV-2 S protein activates intracellular signaling to destabilize ACE2 mRNA. In patients with COVID-19, ACE2 decreased in the pulmonary bronchial region, Ang II level increased in plasma, and pulmonary vascular damage was obvious. The downregulation of ACE2 mediated by Spike protein potentially links COVID-19 to the imbalance of RAS. Summary: 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.