Lysyl Oxidase in Ectopic Cardiovascular Calcification : Role of Oxidative Stress
Ballester-Servera, Carme (Institut de Recerca Sant Pau)
Alonso Nieto, Judith (Institut de Recerca Sant Pau)
Cañes Esteve, Laia (Institut de Recerca Sant Pau)
Vázquez-Sufuentes, Paula (Institut de Recerca Sant Pau)
Garcia Redondo, Ana B.. (Universidad Autónoma de Madrid)
Rodríguez, Cristina (Institut de Recerca Sant Pau)
Martínez-González, José (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2021-122509OB-I00 Instituto de Salud Carlos III PI21/01048
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cardiovascular calcification ; Lysyl oxidase ; Oxidative stress
Publicat a:	Antioxidants, Vol. 13 Núm. 5 (may 2024) , p. 523, ISSN 2076-3921

DOI: 10.3390/antiox13050523
PMID: 38790628

19 p, 7.7 MB

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