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.
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 10M 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.