{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:19:39Z","timestamp":1790752779139,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n (AEI\/MINEICO\/FEDER, UE)","award":["SAF2016-78508-R"],"award-info":[{"award-number":["SAF2016-78508-R"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (AEI\/MINEICO\/FEDER, UE)","award":["PID2020-113634RB-C2"],"award-info":[{"award-number":["PID2020-113634RB-C2"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (AEI\/MINEICO\/FEDER, UE)","award":["2017-SGR1794"],"award-info":[{"award-number":["2017-SGR1794"]}]},{"name":"Association \u201cAutour des Williams\u201d","award":["SAF2016-78508-R"],"award-info":[{"award-number":["SAF2016-78508-R"]}]},{"name":"Association \u201cAutour des Williams\u201d","award":["PID2020-113634RB-C2"],"award-info":[{"award-number":["PID2020-113634RB-C2"]}]},{"name":"Association \u201cAutour des Williams\u201d","award":["2017-SGR1794"],"award-info":[{"award-number":["2017-SGR1794"]}]},{"name":"Generalitat de Catalunya","award":["SAF2016-78508-R"],"award-info":[{"award-number":["SAF2016-78508-R"]}]},{"name":"Generalitat de Catalunya","award":["PID2020-113634RB-C2"],"award-info":[{"award-number":["PID2020-113634RB-C2"]}]},{"name":"Generalitat de Catalunya","award":["2017-SGR1794"],"award-info":[{"award-number":["2017-SGR1794"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Williams\u2013Beuren 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.<\/jats:p>","DOI":"10.3390\/ijms24043261","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:01:45Z","timestamp":1675825305000},"page":"3261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams\u2013Beuren Syndrome Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-6764","authenticated-orcid":false,"given":"Noura","family":"Abdalla","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ortiz-Romero","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-0351","authenticated-orcid":false,"given":"Isaac","family":"Rodriguez-Rovira","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1988-3005","authenticated-orcid":false,"given":"Luis A.","family":"P\u00e9rez-Jurado","sequence":"additional","affiliation":[{"name":"Department of Medicine and Life Sciences, University Pompeu Fabra, 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"},{"name":"Genetics Service, Hospital del Mar & Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5242-150X","authenticated-orcid":false,"given":"Gustavo","family":"Egea","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-2641","authenticated-orcid":false,"given":"Victoria","family":"Campuzano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1056\/NEJMra0903074","article-title":"Williams-Beuren Syndrome","volume":"362","author":"Pober","year":"2010","journal-title":"N. 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