Lysyl Oxidase in Ectopic Cardiovascular Calcification

Ballester-Servera, Carme|||0000-0001-7858-3064; Alonso Nieto, Judith|||0000-0003-0537-0417; Cañes Esteve, Laia|||0000-0002-9579-1321; Vázquez-Sufuentes, Paula|||0009-0001-3369-9087; Garcia Redondo, Ana B.|||0000-0002-5815-3320; Rodríguez, Cristina|||0000-0002-6472-5647; Martínez-González, José|||0000-0002-3894-7166

Lysyl Oxidase in Ectopic Cardiovascular Calcification

Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated...

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Autores:	Ballester-Servera, Carme\|\|\|0000-0001-7858-3064, Alonso Nieto, Judith\|\|\|0000-0003-0537-0417, Cañes Esteve, Laia\|\|\|0000-0002-9579-1321, Vázquez-Sufuentes, Paula\|\|\|0009-0001-3369-9087, Garcia Redondo, Ana B.\|\|\|0000-0002-5815-3320, Rodríguez, Cristina\|\|\|0000-0002-6472-5647, Martínez-González, José\|\|\|0000-0002-3894-7166
Tipo de recurso:	artículo
Fecha de publicación:	2024
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:293370
Acceso en línea:	https://ddd.uab.cat/record/293370 https://dx.doi.org/urn:doi:10.3390/antiox13050523
Access Level:	acceso abierto
Palabra clave:	Cardiovascular calcification Lysyl oxidase Oxidative stress

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spelling	Lysyl Oxidase in Ectopic Cardiovascular CalcificationRole of Oxidative StressBallester-Servera, Carme\|\|\|0000-0001-7858-3064Alonso Nieto, Judith\|\|\|0000-0003-0537-0417Cañes Esteve, Laia\|\|\|0000-0002-9579-1321Vázquez-Sufuentes, Paula\|\|\|0009-0001-3369-9087Garcia Redondo, Ana B.\|\|\|0000-0002-5815-3320Rodríguez, Cristina\|\|\|0000-0002-6472-5647Martínez-González, José\|\|\|0000-0002-3894-7166Cardiovascular calcificationLysyl oxidaseOxidative stressLysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOX) and colocalized with a marker of oxidative stress (8-oxo-deoxyguanosine) in vascular smooth muscle cells (VSMCs). Similarly, in calcific aortic valves, high LOX expression was detected in valvular interstitial cells (VICs) positive for 8-oxo-deoxyguanosine, while LOX and LOXL2 expression correlated with osteogenic markers (SPP1 and RUNX2) and NOX2. In human VICs, mito-TEMPO and TEMPOL attenuated the increase in superoxide anion levels and the mineralization induced by osteogenic media (OM). Likewise, in OM-exposed VICs, β-aminopropionitrile (a LOX inhibitor) ameliorated both oxidative stress and calcification. Gain- and loss-of-function approaches in VICs demonstrated that while LOX silencing negatively modulates oxidative stress and calcification induced by OM, lentiviral LOX overexpression exacerbated oxidative stress and VIC calcification, effects that were prevented by mito-TEMPO, TEMPOL, and β-aminopropionitrile. Our data indicate that LOX-induced oxidative stress participates in the procalcifying effects of LOX activity in ectopic cardiovascular calcification, and highlight the multifaceted role played by LOX isoenzymes in cardiovascular diseases.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/293370https://dx.doi.org/urn:doi:10.3390/antiox13050523reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-122509OB-I00Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/01048open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2933702026-06-06T12:50:31Z
dc.title.none.fl_str_mv	Lysyl Oxidase in Ectopic Cardiovascular Calcification Role of Oxidative Stress
title	Lysyl Oxidase in Ectopic Cardiovascular Calcification
spellingShingle	Lysyl Oxidase in Ectopic Cardiovascular Calcification Ballester-Servera, Carme\|\|\|0000-0001-7858-3064 Cardiovascular calcification Lysyl oxidase Oxidative stress
title_short	Lysyl Oxidase in Ectopic Cardiovascular Calcification
title_full	Lysyl Oxidase in Ectopic Cardiovascular Calcification
title_fullStr	Lysyl Oxidase in Ectopic Cardiovascular Calcification
title_full_unstemmed	Lysyl Oxidase in Ectopic Cardiovascular Calcification
title_sort	Lysyl Oxidase in Ectopic Cardiovascular Calcification
dc.creator.none.fl_str_mv	Ballester-Servera, Carme\|\|\|0000-0001-7858-3064 Alonso Nieto, Judith\|\|\|0000-0003-0537-0417 Cañes Esteve, Laia\|\|\|0000-0002-9579-1321 Vázquez-Sufuentes, Paula\|\|\|0009-0001-3369-9087 Garcia Redondo, Ana B.\|\|\|0000-0002-5815-3320 Rodríguez, Cristina\|\|\|0000-0002-6472-5647 Martínez-González, José\|\|\|0000-0002-3894-7166
author	Ballester-Servera, Carme\|\|\|0000-0001-7858-3064
author_facet	Ballester-Servera, Carme\|\|\|0000-0001-7858-3064 Alonso Nieto, Judith\|\|\|0000-0003-0537-0417 Cañes Esteve, Laia\|\|\|0000-0002-9579-1321 Vázquez-Sufuentes, Paula\|\|\|0009-0001-3369-9087 Garcia Redondo, Ana B.\|\|\|0000-0002-5815-3320 Rodríguez, Cristina\|\|\|0000-0002-6472-5647 Martínez-González, José\|\|\|0000-0002-3894-7166
author_role	author
author2	Alonso Nieto, Judith\|\|\|0000-0003-0537-0417 Cañes Esteve, Laia\|\|\|0000-0002-9579-1321 Vázquez-Sufuentes, Paula\|\|\|0009-0001-3369-9087 Garcia Redondo, Ana B.\|\|\|0000-0002-5815-3320 Rodríguez, Cristina\|\|\|0000-0002-6472-5647 Martínez-González, José\|\|\|0000-0002-3894-7166
author2_role	author author author author author author
dc.contributor.none.fl_str_mv	Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv	Cardiovascular calcification Lysyl oxidase Oxidative stress
topic	Cardiovascular calcification Lysyl oxidase Oxidative stress
description	Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOX) and colocalized with a marker of oxidative stress (8-oxo-deoxyguanosine) in vascular smooth muscle cells (VSMCs). Similarly, in calcific aortic valves, high LOX expression was detected in valvular interstitial cells (VICs) positive for 8-oxo-deoxyguanosine, while LOX and LOXL2 expression correlated with osteogenic markers (SPP1 and RUNX2) and NOX2. In human VICs, mito-TEMPO and TEMPOL attenuated the increase in superoxide anion levels and the mineralization induced by osteogenic media (OM). Likewise, in OM-exposed VICs, β-aminopropionitrile (a LOX inhibitor) ameliorated both oxidative stress and calcification. Gain- and loss-of-function approaches in VICs demonstrated that while LOX silencing negatively modulates oxidative stress and calcification induced by OM, lentiviral LOX overexpression exacerbated oxidative stress and VIC calcification, effects that were prevented by mito-TEMPO, TEMPOL, and β-aminopropionitrile. Our data indicate that LOX-induced oxidative stress participates in the procalcifying effects of LOX activity in ectopic cardiovascular calcification, and highlight the multifaceted role played by LOX isoenzymes in cardiovascular diseases.
publishDate	2024
dc.date.none.fl_str_mv	2 2024-01-01 2024 2024-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/293370 https://dx.doi.org/urn:doi:10.3390/antiox13050523
url	https://ddd.uab.cat/record/293370 https://dx.doi.org/urn:doi:10.3390/antiox13050523
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-122509OB-I00 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/01048
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
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Lysyl Oxidase in Ectopic Cardiovascular Calcification

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