Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta - Université Grenoble Alpes Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta

Olfa Harki
  • Fonction : Auteur
  • PersonId : 1144666
Alejandro Arco-Hierves
Alexandra Demory
Carole Chirica
  • Fonction : Auteur
Isabelle Vilgrain
  • Fonction : Auteur
Jean-Louis Pépin
  • Fonction : Auteur
  • PersonId : 1093730

Résumé

Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induc-es atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS pa-tients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and re-sults in endothelial hyperpermeability. Our aim was to determine whether blocking VE-cadherin cleavage in vivo could be an efficient strategy to inhibit deleterious IH-induced vascular remodeling, elastic fiber defects and atherogenesis. VE-cadherin regulation, aortic re-modeling and atherosclerosis were studied in IH-exposed C57Bl/6J or Ap-oE-/- mice treated or not with Src-tyr-kinases inhibitors (Saracat-inib/Pazopanib) or a HIF-1 inhibitor (Acriflavine). Human aortic endothelial cells were exposed to IH and treated with the same inhibitors. LDL and the monocytes transendothelium passage were measured. In vitro, IH increased transendothelium LDL and monocytes passage, and the tested inhibitors prevented these effects. In mice, IH decreased VE-cadherin expression and in-creased plasmatic sVE level, intima-media thickness, elastic fiber alterations and atherosclerosis, while the inhibitors prevented these in vivo effects. In vivo inhibition of HIF-1 and Src tyr ki-nase pathways were associated with the prevention of IH-induced elastic fiber/lamella degrada-tion and atherogenesis, which suggests that VE-cadherin could be an important target to limit atherogenesis and progression of arterial stiffness in OSAS.
Fichier principal
Vignette du fichier
Harki 2022 version finale.pdf (1.39 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03703694 , version 1 (24-06-2022)

Identifiants

Citer

Olfa Harki, Sophie Bouyon, Marine Sallé, Alejandro Arco-Hierves, Emeline Lemarié, et al.. Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta. International Journal of Molecular Sciences, 2022, 23 (13), pp.7012. ⟨10.3390/ijms23137012⟩. ⟨hal-03703694⟩
34 Consultations
15 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More