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Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

Molecular Mechanisms of Endothelialitis in SARS-CoV-2 Infection: Evidence for VE-Cadherin Cleavage by ACE2

Laurence Bouillet
Alban Deroux
Meryem Benmarce
  • Fonction : Auteur
Chloé Guérin
  • Fonction : Auteur
Laura Bouvet
  • Fonction : Auteur

Résumé

Long COVID-19 syndrome appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damage to microcapillaries, microthrombi, and endothelialitis. However, the mechanisms involved in these processes remain to be elucidated. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium, which provides a the major function is to prevent coagulation. A component of endothelial cell junctions is VE-cadherin, which is responsible for maintaining the integrity of the vessels through homophilic interactions of its Ca++-dependent adhesive extracellular domain. Here we provide the first 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 positions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ectopeptidase hrACE2 for 16 hrs in the presence of 10 μM ZnCl2 showed a dose-dependent (from 0.2 ng/μL to 2 ng/μL) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19 we detected a circulating form of ACE2 with an apparent molecular mass of 70 kDa, which was barely detectable in patients with mild COVID-19. 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 to cleave VE-cadherin, which leads to potential biomarkers of SARS-CoV-2 infection related with the vascular disease in “Long COVID-19”.

Dates et versions

hal-04236746 , version 1 (11-10-2023)

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Citer

Laurence Bouillet, Alban Deroux, Meryem Benmarce, Chloé Guérin, Laura Bouvet, et al.. Molecular Mechanisms of Endothelialitis in SARS-CoV-2 Infection: Evidence for VE-Cadherin Cleavage by ACE2. International Journal of Molecular Sciences, 2023, 24 (15), pp.12525. ⟨10.3390/ijms241512525⟩. ⟨hal-04236746⟩
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