Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
Rodríguez-Rovira, Isaac (Universitat de Barcelona)
López-Sainz, Angela (Hospital Clínic i Provincial de Barcelona)
Palomo-Buitrago, Maria Encarnación (Universitat de Barcelona)
Pérez, Belén (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Jiménez Altayó, Francesc (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Campuzano, Victoria (Universitat de Barcelona)
Egea, Gustavo (Universitat de Barcelona)

Fecha:	2023
Descripción:	15 pàg.
Resumen:	Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor, blocked aortopathy in a MFS mouse model acting as an antioxidant without altering uric acid (UA) plasma levels. Hyperuricaemia is ambiguously associated with cardiovascular injuries as UA, having antioxidant or pro-oxidant properties depending on the concentration and accumulation site. We aimed to evaluate whether hyperuricaemia causes harm or relief in MFS aortopathy pathogenesis. Two-month-old male wild-type (WT) and MFS mice (Fbn1C1041G/+) were injected intraperitoneally for several weeks with potassium oxonate (PO), an inhibitor of uricase (an enzyme that catabolises UA to allantoin). Plasma UA and allantoin levels were measured via several techniques, aortic root diameter and cardiac parameters by ultrasonography, aortic wall structure by histopathology, and pNRF2 and 3-NT levels by immunofluorescence. PO induced a significant increase in UA in blood plasma both in WT and MFS mice, reaching a peak at three and four months of age but decaying at six months. Hyperuricaemic MFS mice showed no change in the characteristic aortic aneurysm progression or aortic wall disarray evidenced by large elastic laminae ruptures. There were no changes in cardiac parameters or the redox stress-induced nuclear translocation of pNRF2 in the aortic tunica media. Altogether, the results suggest that hyperuricaemia interferes neither with aortopathy nor cardiopathy in MFS mice.
Ayudas:	Agencia Estatal de Investigación PID2020-113634RB-C2
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Uric acid ; Aortic aneurysm ; Marfan syndrome ; Allopurinol ; Oxidative stress ; Oxonic acid ; Hyperuricaemia
Publicado en:	International journal of molecular sciences, Vol. 24 Núm. 14 (2023) , p. 11293, ISSN 1422-0067

DOI: 10.3390/ijms241411293
PMID: 37511051

15 p, 2.4 MB

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