Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Infection: Molecular Mechanisms of Endothelial Dysfunction in COVID-19 Patients

Laurence Bouillet
ORCID logo ,
Alban DEROUX
ORCID logo ,
Meryem BENMARCE
,
Chloé GUERIN
,
Laura BOUVET
,
Olivia GARNIER
,
Donald K. MARTIN
,
ISABELLE VILGRAIN
* ORCID logo
Version 1 : Received: 8 June 2023 / Approved: 9 June 2023 / Online: 9 June 2023 (03:43:57 CEST)

A peer-reviewed article of this Preprint also exists.

Bouillet, L.; Deroux, A.; Benmarce, M.; Guérin, C.; Bouvet, L.; Garnier, O.; Martin, D.K.; Vilgrain, I. Molecular Mechanisms of Endothelialitis in SARS-CoV-2 Infection: Evidence for VE-Cadherin Cleavage by ACE2. Int. J. Mol. Sci. 2023, 24, 12525. Bouillet, L.; Deroux, A.; Benmarce, M.; Guérin, C.; Bouvet, L.; Garnier, O.; Martin, D.K.; Vilgrain, I. Molecular Mechanisms of Endothelialitis in SARS-CoV-2 Infection: Evidence for VE-Cadherin Cleavage by ACE2. Int. J. Mol. Sci. 2023, 24, 12525.

Abstract

Long COVID-19 syndrom appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damages to microcapillaries, microthombi and endotheliitis. However, the mech-anisms involved in these processes remain to be identified. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium of which one of the major properties is to prevent coagulation. VE cadherin is a component of endothelial cell junctions responsible for maintenance of the integrity of the vessels through homophilic interaction of its Ca++- dependent adhesive extracellular domain. We first provide evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the po-sitions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ecto-peptidase hrACE2 for 16 hrs in the presence of 10M ZnCl2 showed a dose-dependent (from 0.2 ng/ul to 2 ng/ul) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19, a circulating form of ACE2 was detected with an apparent molecular mass of 70 kDa while it was barely detectable in patients with mild infection. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 on VE-cadherin cleavage leading to potential biomarkers in SARS-CoV2 infection related with the vascular disease in “Long COVID-19”.

Keywords

Endothelium; VE-cadherin; ACE2; SARS-CoV2 infection; Long COVID syndrome

Subject

Medicine and Pharmacology, Internal Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.