Lysyl oxidase (LOX) limits VSMC proliferation and neointimal thickening through its extracellular enzymatic activity
Varona, Saray (Institut d'Investigació Biomèdica Sant Pau)
Orriols, Mar (Institut d'Investigació Biomèdica Sant Pau)
Galán, María (Institut d'Investigació Biomèdica Sant Pau)
Guadall, Anna (Institut d'Investigació Biomèdica Sant Pau)
Cañes Esteve, Laia (Institut d'Investigació Biomèdica Sant Pau)
Aguiló, Silvia (Institut d'Investigació Biomèdica Sant Pau)
Sirvent, Marc (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez-González, José (Institut d'Investigació Biomèdica Sant Pau)
Rodríguez, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Lysyl oxidase (LOX) plays a critical role in extracellular matrix maturation and limits VSMC proliferation and vascular remodeling. We have investigated whether this anti-proliferative effect relies on the extracellular catalytically active LOX or on its biologically active propeptide (LOX-PP). High expression levels of both LOX and LOX-PP were detected in the vascular wall from transgenic mice over-expressing the full-length human LOX cDNA under the control of SM22α promoter (TgLOX), which targets the transgene to VSMC without affecting the expression of mouse LOX isoenzymes. TgLOX VSMC also secrete high amounts of both mature LOX and LOX-PP. Wild-type (WT) mouse VSMC exposed to VSMC supernatants from transgenic animals showed reduced proliferative rates (low [H]-thymidine uptake and expression of PCNA) than those incubated with conditioned media from WT cells, effect that was abrogated by β-aminopropionitrile (BAPN), an inhibitor of LOX activity. Lentiviral over-expression of LOX, but not LOX-PP, decreased human VSMC proliferation, effect that was also prevented by BAPN. LOX transgenesis neither impacted local nor systemic inflammatory response induced by carotid artery ligation. Interestingly, in this model, BAPN normalized the reduced neointimal thickening observed in TgLOX mice. Therefore, extracellular enzymatically active LOX is required to limit both VSMC proliferation and vascular remodeling.
Grants:	Ministerio de Economía y Competitividad PI15/01016 Ministerio de Economía y Competitividad SAF2015-64767-R
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 8 Núm. 1 (january 2018) , p. 13258, ISSN 2045-2322

DOI: 10.1038/s41598-018-31312-w
PMID: 30185869

10 p, 4.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles