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Spike-mediated ACE2 down-regulation involved in the pathogenesis of SARS-CoV-2 infection.


ABSTRACT: 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 patient. Our finding indicates that the downregulation of ACE2 potentially links COVID-19 to the imbalance of RAS.

SUBMITTER: Gao X 

PROVIDER: S-EPMC9250808 | biostudies-literature |

REPOSITORIES: biostudies-literature

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