Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress
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...
| Autores: | ; ; ; ; ; ; |
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| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositório: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p17968 |
| Acesso em linha: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17968 http://ddd.uab.cat/record/293370 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | lysyl oxidase oxidative stress cardiovascular calcification |
| _version_ | 1878736986194313216 |
|---|---|
| author | Ballester-Servera, C |
| author2 | Alonso, J Cañes, L Vázquez-Sufuentes, P García-Redondo, AB Rodríguez, C Martínez-González, J |
| author2_role | author author author author author author |
| author_browse | Alonso, J Ballester-Servera, C Cañes, L García-Redondo, AB Martínez-González, J Rodríguez, C Vázquez-Sufuentes, P |
| author_facet | Ballester-Servera, C Alonso, J Cañes, L Vázquez-Sufuentes, P García-Redondo, AB Rodríguez, C Martínez-González, J |
| author_role | author |
| collection | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| 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 (TgLOXVSMC) 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, beta-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 beta-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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_9893c141b7bc81bfd6bd71412ac36088 |
| institution | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| instname_str | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:iibsantpau.fundanetsuite.com:p17968 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| spelling | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress Ballester-Servera, C Alonso, J Cañes, L Vázquez-Sufuentes, P García-Redondo, AB Rodríguez, C Martínez-González, J lysyl oxidase oxidative stress 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 in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOXVSMC) 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, beta-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 beta-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. MDPI https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17968 http://ddd.uab.cat/record/293370 |
| spellingShingle | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress Ballester-Servera, C lysyl oxidase oxidative stress cardiovascular calcification |
| status_str | publishedVersion |
| title | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| title_full | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| title_fullStr | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| title_full_unstemmed | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| title_short | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| title_sort | Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress |
| topic | lysyl oxidase oxidative stress cardiovascular calcification |
| topic_facet | lysyl oxidase oxidative stress cardiovascular calcification |
| url | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17968 http://ddd.uab.cat/record/293370 |