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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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11293 |
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| author | Isaac Rodríguez-Rovira Angela López-Sainz Maria Encarnación Palomo-Buitrago Belen Pérez Francesc Jiménez-Altayó Victoria Campuzano Gustavo Egea |
| author_facet | Isaac Rodríguez-Rovira Angela López-Sainz Maria Encarnación Palomo-Buitrago Belen Pérez Francesc Jiménez-Altayó Victoria Campuzano Gustavo Egea |
| author_sort | Isaac Rodríguez-Rovira |
| collection | DOAJ |
| 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 (<i>Fbn1<sup>C1041G/+</sup></i>) 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. |
| first_indexed | 2024-03-11T01:01:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:01:49Z |
| publishDate | 2023-07-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-928502543dab4514832e91d0b751efc62023-11-18T19:37:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141129310.3390/ijms241411293Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan SyndromeIsaac Rodríguez-Rovira0Angela López-Sainz1Maria Encarnación Palomo-Buitrago2Belen Pérez3Francesc Jiménez-Altayó4Victoria Campuzano5Gustavo Egea6Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainDepartment of Cardiology, Hospital Clínic de Barcelona, IDIBAPS, 08036 Barcelona, SpainDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainDepartment of Pharmacology, School of Medicine, Autonomous University of Barcelona, Bellaterra, 08192 Barcelona, SpainDepartment of Pharmacology, School of Medicine, Autonomous University of Barcelona, Bellaterra, 08192 Barcelona, SpainDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, SpainRedox 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 (<i>Fbn1<sup>C1041G/+</sup></i>) 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.https://www.mdpi.com/1422-0067/24/14/11293uric acidaortic aneurysmMarfan syndromeallopurinoloxidative stressoxonic acid |
| spellingShingle | Isaac Rodríguez-Rovira Angela López-Sainz Maria Encarnación Palomo-Buitrago Belen Pérez Francesc Jiménez-Altayó Victoria Campuzano Gustavo Egea Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome International Journal of Molecular Sciences uric acid aortic aneurysm Marfan syndrome allopurinol oxidative stress oxonic acid |
| 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 | uric acid aortic aneurysm Marfan syndrome allopurinol oxidative stress oxonic acid |
| url | https://www.mdpi.com/1422-0067/24/14/11293 |
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