SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

  1. Yuyang Lei
  2. Jiao Zhang
  3. Cara R. Schiavon
  4. Ming He
  5. Lili Chen
  6. Hui Shen
  7. Yichi Zhang
  8. Qian Yin
  9. Yoshitake Cho
  10. Leonardo Andrade
  11. Gerry S. Shadel
  12. Mark Hepokoski
  13. Ting Lei
  14. Hongliang Wang
  15. Jin Zhang
  16. Jason X.-J. Yuan
  17. Atul Malhotra
  18. Uri Manor
  19. Shengpeng Wang
  20. Zu-Yi Yuan
  21. John Y-J. Shyy

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Abstract

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

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    SciScore for 10.1101/2020.12.04.409144: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.12.04.409144 on bioRxiv