Cargando…

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

Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induces atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS patients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and results in endothel...

Descripción completa

Detalles Bibliográficos
Autores principales: Harki, Olfa, Bouyon, Sophie, Sallé, Marine, Arco-Hierves, Alejandro, Lemarié, Emeline, Demory, Alexandra, Chirica, Carole, Vilgrain, Isabelle, Pépin, Jean-Louis, Faury, Gilles, Briançon-Marjollet, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266969/
https://www.ncbi.nlm.nih.gov/pubmed/35806017
http://dx.doi.org/10.3390/ijms23137012
_version_ 1784743601039736832
author Harki, Olfa
Bouyon, Sophie
Sallé, Marine
Arco-Hierves, Alejandro
Lemarié, Emeline
Demory, Alexandra
Chirica, Carole
Vilgrain, Isabelle
Pépin, Jean-Louis
Faury, Gilles
Briançon-Marjollet, Anne
author_facet Harki, Olfa
Bouyon, Sophie
Sallé, Marine
Arco-Hierves, Alejandro
Lemarié, Emeline
Demory, Alexandra
Chirica, Carole
Vilgrain, Isabelle
Pépin, Jean-Louis
Faury, Gilles
Briançon-Marjollet, Anne
author_sort Harki, Olfa
collection PubMed
description Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induces atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS patients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and results 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 remodeling and atherosclerosis were studied in IH-exposed C57Bl/6J or ApoE-/-mice treated or not with Src-tyr-kinases inhibitors (Saracatinib/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 increased 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 kinase pathways were associated with the prevention of IH-induced elastic fiber/lamella degradation and atherogenesis, which suggests that VE-cadherin could be an important target to limit atherogenesis and progression of arterial stiffness in OSAS.
format Online
Article
Text
id pubmed-9266969
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92669692022-07-09 Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta Harki, Olfa Bouyon, Sophie Sallé, Marine Arco-Hierves, Alejandro Lemarié, Emeline Demory, Alexandra Chirica, Carole Vilgrain, Isabelle Pépin, Jean-Louis Faury, Gilles Briançon-Marjollet, Anne Int J Mol Sci Article Intermittent hypoxia (IH), the major feature of obstructive sleep apnea syndrome (OSAS), induces atherosclerosis and elastic fiber alterations. VE-cadherin cleavage is increased in OSAS patients and in an IH-cellular model. It is mediated by HIF-1 and Src-tyr-kinases pathways and results 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 remodeling and atherosclerosis were studied in IH-exposed C57Bl/6J or ApoE-/-mice treated or not with Src-tyr-kinases inhibitors (Saracatinib/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 increased 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 kinase pathways were associated with the prevention of IH-induced elastic fiber/lamella degradation and atherogenesis, which suggests that VE-cadherin could be an important target to limit atherogenesis and progression of arterial stiffness in OSAS. MDPI 2022-06-24 /pmc/articles/PMC9266969/ /pubmed/35806017 http://dx.doi.org/10.3390/ijms23137012 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Harki, Olfa
Bouyon, Sophie
Sallé, Marine
Arco-Hierves, Alejandro
Lemarié, Emeline
Demory, Alexandra
Chirica, Carole
Vilgrain, Isabelle
Pépin, Jean-Louis
Faury, Gilles
Briançon-Marjollet, Anne
Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title_full Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title_fullStr Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title_full_unstemmed Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title_short Inhibition of Vascular Endothelial Cadherin Cleavage Prevents Elastic Fiber Alterations and Atherosclerosis Induced by Intermittent Hypoxia in the Mouse Aorta
title_sort inhibition of vascular endothelial cadherin cleavage prevents elastic fiber alterations and atherosclerosis induced by intermittent hypoxia in the mouse aorta
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266969/
https://www.ncbi.nlm.nih.gov/pubmed/35806017
http://dx.doi.org/10.3390/ijms23137012
work_keys_str_mv AT harkiolfa inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT bouyonsophie inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT sallemarine inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT arcohiervesalejandro inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT lemarieemeline inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT demoryalexandra inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT chiricacarole inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT vilgrainisabelle inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT pepinjeanlouis inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT faurygilles inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta
AT brianconmarjolletanne inhibitionofvascularendothelialcadherincleavagepreventselasticfiberalterationsandatherosclerosisinducedbyintermittenthypoxiainthemouseaorta