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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/193718
The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams-Beuren Syndrome Mouse Model
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Williams-Beuren syndrome (WBS) is a rare disorder caused by a recurrent microdeletion with hallmarks of cardiovascular manifestations, mainly supra-valvular aortic stenosis (SVAS). Unfortunately, there is currently no efficient treatment. We investigated the effect of chronic oral treatment with curcumin and verapamil on the cardiovascular phenotype of a murine model of WBS harbouring a similar deletion, CD (complete deletion) mice. We analysed systolic blood pressure in vivo and the histopathology of the ascending aorta and the left ventricular myocardium to determine the effects of treatments and their underlying mechanism. Molecular analysis showed significantly upregulated xanthine oxidoreductase (XOR) expression in the aorta and left ventricular myocardium of CD mice. This overexpression is concomitant with increased levels of nitrated proteins as a result of byproduct-mediated oxidative stress damage, indicating that XOR-generated oxidative stress impacts the pathophysiology of cardiovascular manifestations in WBS. Only the combined therapy of curcumin and verapamil resulted in a significant improvement of cardiovascular parameters via activation of the nuclear factor erythroid 2 (NRF2) and reduction of XOR and nitrated protein levels. Our data suggested that the inhibition of XOR and oxidative stress damage could help prevent the severe cardiovascular injuries of this disorder.
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ABDALLA, Noura, ORTIZ ROMERO, Paula, RODRÍGUEZ ROVIRA, Isaac, PÉREZ JURADO, Luis a., EGEA GURI, Gustavo, CAMPUZANO UCEDA, María victoria. The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams-Beuren Syndrome Mouse Model. _International Journal of Medical Sciences_. 2023. Vol. 24, núm. 3261. [consulta: 26 de febrer de 2026]. ISSN: 1449-1907. [Disponible a: https://hdl.handle.net/2445/193718]