Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren syndrome.

CAMPUZANO, V; SEGURA-PUIMEDON, M; TERRADO, V; SÁNCHEZ-RODRÍGUEZ, C; COUSTETS, M; MAURICIO ARIEL MENACHO; NEVADO, J; XOSÉ R. BUSTELO; FRANCKE, U; PÉREZ-JURADO, L

PLOS GENETICS

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 8 p. 1002458 - 1002458

1553-7390

Williams-Beuren Syndrome (WBS) is a rare developmental disorder characterized by distinctive facial, neurobehavioral, and cardiovascular features, caused by a heterozygous loss of genetic material (deletion) at the 7q11.23 chromosomal band. Elastin protein deficiency, due to deletion of one copy of the ELN gene, is responsible for developmental anomalies in arterial wall remodeling, predisposing WBS patients to high blood pressure and other serious cardiovascular complications. We have previously shown that a fraction of WBS patients who lack a copy of the NCF1 gene, which codes for p47phox, a subunit of NADPH-oxidase (NOX), have lower cardiovascular risk associated with decreased oxidative stress. Here, we used a mouse model of elastin deficiency to better define the contribution of NOX–mediated oxidative stress to the cardiovascular phenotype of WBS and to confirm the role of Ncf1 as a major modulator. In addition, pharmacological inhibition of NOX activation or synthesis with either losartan or apocynin significantly rescued the cardiovascular phenotype of these mice, suggesting that these drugs should also be evaluated in human patients.