Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress
Por:
Ballester-Servera, C, Alonso, J, Cañes, L, Vázquez-Sufuentes, P, García-Redondo, AB, Rodríguez, C, Martínez-González, J
Publicada:
1 may 2024
Resumen:
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.
Filiaciones:
Ballester-Servera, C:
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona 08036, Spain
Inst Salud Carlos III, CIBER Enfermedades Cardiovasc, Madrid 28029, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
Alonso, J:
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona 08036, Spain
Inst Salud Carlos III, CIBER Enfermedades Cardiovasc, Madrid 28029, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
Cañes, L:
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona 08036, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
Vázquez-Sufuentes, P:
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona 08036, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
García-Redondo, AB:
Inst Salud Carlos III, CIBER Enfermedades Cardiovasc, Madrid 28029, Spain
Univ Autonoma Madrid, Inst Invest Hosp La Paz, Madrid 28029, Spain
Rodríguez, C:
Inst Salud Carlos III, CIBER Enfermedades Cardiovasc, Madrid 28029, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
Martínez-González, J:
Consejo Super Invest Cient IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona 08036, Spain
Inst Salud Carlos III, CIBER Enfermedades Cardiovasc, Madrid 28029, Spain
Inst Recerca St Pau IR St PAU, Barcelona 08041, Spain
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