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Publication Detail
SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction
  • Publication Type:
    Journal article
  • Authors:
    Hirunpattarasilp C, James G, Kwanthongdee J, Freitas F, Huo J, Sethi H, Kittler JT, Owens RJ, McCoy LE, Attwell D
  • Publisher:
    Oxford University Press (OUP)
  • Publication date:
    22/07/2022
  • Journal:
    Brain
  • Medium:
    Print-Electronic
  • Status:
    Accepted
  • Country:
    England
  • Print ISSN:
    0006-8950
  • PII:
    6648726
  • Language:
    English
  • Keywords:
    SARS-CoV-2, capillary, pericyte
  • Notes:
    Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II evoked a small pericyte-mediated capillary constriction via AT1 receptors, but evoked a large constriction when the SARS-CoV-2 receptor binding domain (RBD, original Wuhan variant) was present. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices, and was evoked in hamster brain slices by pseudotyped virions expressing SARS-CoV-2 spike protein. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7) mediated by removal of ACE2 from the cell surface membrane, and was mimicked by blocking ACE2. The clinically-used drug losartan inhibited the RBD-potentiated constriction. Thus, AT1 receptor blockers could be protective in Covid-19 by preventing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.
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UCL GOS Institute of Child Health
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Neuro, Physiology & Pharmacology
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