The combined treatment of curcumin with verapamil ameliorates the cardiovascular pathology in a Williams-Beuren syndrome mouse model
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- dc.contributor.author Abdalla, Noura
- dc.contributor.author Ortiz Romero, Paula, 1994-
- dc.contributor.author Rodriguez-Rovira, Isaac
- dc.contributor.author Pérez Jurado, Luis Alberto
- dc.contributor.author Egea, Gustavo
- dc.contributor.author Campuzano Uceda, María Victoria
- dc.date.accessioned 2023-05-19T06:03:02Z
- dc.date.available 2023-05-19T06:03:02Z
- dc.date.issued 2023
- dc.description.abstract 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.
- dc.description.sponsorship This research was funded by Ministerio de Ciencia e Innovación (AEI/MINEICO/FEDER, UE), grant number: SAF2016-78508-R to V.C. and PID2020-113634RB-C2 to G.E.; from Association “Autour des Williams” to V.C.; and Generalitat de Catalunya (2017-SGR1794) to L.A.P.J.
- dc.format.mimetype application/pdf
- dc.identifier.citation Abdalla N, Ortiz-Romero P, Rodriguez-Rovira I, Pérez-Jurado LA, Egea G, Campuzano V. The combined treatment of curcumin with verapamil ameliorates the cardiovascular pathology in a Williams-Beuren syndrome mouse model. Int J Mol Sci. 2023 Feb 7;24(4):3261. DOI: 10.3390/ijms24043261
- dc.identifier.doi http://dx.doi.org/10.3390/ijms24043261
- dc.identifier.issn 1422-0067
- dc.identifier.uri http://hdl.handle.net/10230/56897
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Int J Mol Sci. 2023 Feb 7;24(4):3261
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-78508-R
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-113634RB-C2
- dc.rights © 2023 by the authors. 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword CD mice
- dc.subject.keyword Williams-Beuren syndrome
- dc.subject.keyword Cardiovascular disease
- dc.subject.keyword Curcumin
- dc.subject.keyword Oxidative stress
- dc.subject.keyword Verapamil
- dc.title The combined treatment of curcumin with verapamil ameliorates the cardiovascular pathology in a Williams-Beuren syndrome mouse model
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion