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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Enfermedad vascular hipertensiva > DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista >

Functional Effect of the p22phox -930A/G Polymorphism on p22phox Expression and NADPH Oxidase Activity in Hypertension
Autor(es) : San-Jose, G. (Gorka)
Moreno, M.U. (María Ujué)
Olivan, S. (Sara)
Beloqui, O. (Óscar)
Fortuño, A. (Ana)
Diez, J. (Javier)
Zalba, G. (Guillermo)
Palabras clave : Hypertension arterial
Oxidative stress
Polymorphism
Fecha incorporación: ago-2004
Editorial : American Heart Association
Versión del editor: http://hyper.ahajournals.org/cgi/content/full/44/2/163
ISSN: 1524-4563
Cita: San José G, Moreno MU, Oliván S, Beloqui O, Fortuño A, Díez J, et al. Functional effect of the p22(phox) -930(A/G) polymorphism on p22(phox) expression and NADPH oxidase activity in hypertension. Hypertension 2004 AUG;44(2):163-169.
Resumen
Oxidative stress induced by superoxide is implicated in hypertension. NADPH oxidase is the main source of superoxide in phagocytic and vascular cells, and the p22phox subunit is involved in NADPH oxidase activation. Recently we reported an association of 930A/G polymorphism in the human p22phox gene promoter with hypertension. This study was designed to investigate the functional role of this polymorphism in hypertension. We thus investigated the relationships between the 930A/G polymorphism and p22phox expression and NADPH oxidase–mediated superoxide production in phagocytic cells from 70 patients with essential hypertension and 70 normotensive controls. Genotyping of the polymorphism was performed by restriction fragment length polymorphism. NADPH oxidase activity was determined by chemiluminescence assays, and p22phox mRNA and protein expression was measured by Northern and Western blotting, respectively. Compared with hypertensive subjects with the AA/AG genotype, hypertensive subjects with the GG genotype exhibited increased (P 0.05) phagocytic p22phox mRNA (1.26 0.06 arbitrary unit [AU] versus 0.99 0.03 AU) and protein levels (0.58 0.05 AU versus 0.34 0.04 AU) and enhanced NADPH oxidase activity (1998 181 counts/s versus 1322 112 counts/s). No differences in these parameters were observed among genotypes in normotensive cells. Transfection experiments on vascular smooth muscle cells showed that the A-to-G substitution of this polymorphism produced an increased reporter gene expression in hypertensive cells. Nitric oxide production, as assessed by measurement of serum nitric oxide metabolites, was lower in GG hypertensive subjects than in AA/AG hypertensive subjects. In conclusion, these results suggest that hypertensive subjects carrying the GG genotype of the p22phox 930A/G polymorphism are highly exposed to NADPH oxidase-mediated oxidative stress.
Enlace permanente: http://hdl.handle.net/10171/17836
Aparece en las colecciones: DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista
DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista

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Fichero:  2004 San José et al Hypertension 2004.pdf
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