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SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction.
Hirunpattarasilp, Chanawee; James, Greg; Kwanthongdee, Jaturon; Freitas, Felipe; Huo, Jiandong; Sethi, Huma; Kittler, Josef T; Owens, Raymond J; McCoy, Laura E; Attwell, David.
  • Hirunpattarasilp C; Department of Neuroscience, Physiology & Pharmacology, University College London, London, WC1E 6BT, UK.
  • James G; Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand.
  • Kwanthongdee J; Department of Neuroscience, Physiology & Pharmacology, University College London, London, WC1E 6BT, UK.
  • Freitas F; Department of Neurosurgery, Great Ormond Street Hospital, London, WC1N 3JH, UK.
  • Huo J; Department of Neuroscience, Physiology & Pharmacology, University College London, London, WC1E 6BT, UK.
  • Sethi H; Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand.
  • Kittler JT; Department of Neuroscience, Physiology & Pharmacology, University College London, London, WC1E 6BT, UK.
  • Owens RJ; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK.
  • McCoy LE; Protein Production UK, The Research Complex at Harwell, and Rosalind Franklin Institute, Harwell Science & Innovation Campus, Didcot, OX11 0GD, UK.
  • Attwell D; National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Brain ; 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-2241469
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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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Year: 2022 Document Type: Article Affiliation country: Brain

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Year: 2022 Document Type: Article Affiliation country: Brain