NADPH oxidase-mediated oxidative stress: genetic studies of the p22(phox) gene in hypertension.
Increased vascular production of reactive oxygen species, especially superoxide anion, significantly contributes to the oxidative stress associated with hypertension. An enhanced superoxide production causes an increased inactivation of nitric oxide that diminishes nitric oxide bioavailability, thus contributing to endothelial dysfunction and hypertrophy of vascular cells. It has been shown that NADPH oxidases play a major role as the most important sources of superoxide anion in phagocytic and vascular cells. Several experimental observations have described an enhanced superoxide generation as a result of NADPH oxidase activation in hypertension. Although these enzymes respond to stimuli such as vasoactive factors, growth factors, and cytokines, recent data suggest a significant role of the genetic background in the modulation of the expression of its different components. Several polymorphisms have been identified in the promoter and in the coding region of CYBA, the gene that encodes the essential subunit of the NADPH oxidase p22phox, some of which seem to influence significantly the activity of these enzymes in the context of cardiovascular diseases. Among CYBA polymorphisms, genetic investigations have provided a novel marker, the -930(A/G) polymorphism, which determines the genetic susceptibility of hypertensive patients to oxidative stress.
Zalba
Guillermo
G
Area of Cardiovascular Pathophysiology, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain. gzalba@unav.es
San José
Gorka
G
Moreno
María U
MU
Fortuño
Ana
A
Díez
Javier
J
D000818:Animals; D006801:Humans; D006973:Hypertension; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008957:Models, Genetic; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism*; D011110:Polymorphism, Genetic; D051381:Rats
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human