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Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome

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 ambiguo...

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Autores principales: Rodríguez-Rovira, Isaac, López-Sainz, Angela, Palomo-Buitrago, Maria Encarnación, Pérez, Belen, Jiménez-Altayó, Francesc, Campuzano, Victoria, Egea, Gustavo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379183/
https://www.ncbi.nlm.nih.gov/pubmed/37511051
http://dx.doi.org/10.3390/ijms241411293
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author Rodríguez-Rovira, Isaac
López-Sainz, Angela
Palomo-Buitrago, Maria Encarnación
Pérez, Belen
Jiménez-Altayó, Francesc
Campuzano, Victoria
Egea, Gustavo
author_facet Rodríguez-Rovira, Isaac
López-Sainz, Angela
Palomo-Buitrago, Maria Encarnación
Pérez, Belen
Jiménez-Altayó, Francesc
Campuzano, Victoria
Egea, Gustavo
author_sort Rodríguez-Rovira, Isaac
collection PubMed
description 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 (Fbn1(C1041G/+)) 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.
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spelling pubmed-103791832023-07-29 Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome Rodríguez-Rovira, Isaac López-Sainz, Angela Palomo-Buitrago, Maria Encarnación Pérez, Belen Jiménez-Altayó, Francesc Campuzano, Victoria Egea, Gustavo Int J Mol Sci Article 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 (Fbn1(C1041G/+)) 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. MDPI 2023-07-10 /pmc/articles/PMC10379183/ /pubmed/37511051 http://dx.doi.org/10.3390/ijms241411293 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rodríguez-Rovira, Isaac
López-Sainz, Angela
Palomo-Buitrago, Maria Encarnación
Pérez, Belen
Jiménez-Altayó, Francesc
Campuzano, Victoria
Egea, Gustavo
Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title_full Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title_fullStr Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title_full_unstemmed Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title_short Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome
title_sort hyperuricaemia does not interfere with aortopathy in a murine model of marfan syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379183/
https://www.ncbi.nlm.nih.gov/pubmed/37511051
http://dx.doi.org/10.3390/ijms241411293
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