Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

Abstract

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder with hallmarks in the cardiovascular manifestations and no well-defined therapeutic strategies. We investigated the progression of cardiovascular phenotype present in CD (complete deletion) mice, a murine model of WBS, after chronic treatment with curcumin and verapamil, both compounds with positive effects on related pathologies. Treatment was administered orally dissolved in drinking water. After measuring in-vivo systolic blood pressure, aortic and left ventricular myocardium were histological and molecular analysed to determine the effects of treatment and its underlying mechanism in CD mice. We observed upregulated xanthine oxidoreductase (XOR) expression in both aortic and left ventricular myocardium of CD mice. This overexpression is concomitant with increased levels of nitrated proteins as example of byproduct-mediated oxidative stress damage, indicating of XOR-generated oxidative stress impact on the pathophysiology of cardiovascular manifestations in WBS, and suggesting that the inhibition of XOR and/or oxidative stress damage could help to ameliorate the severe cardiovascular injuries presented in WBS.