Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants.
Several risk factors for coronary artery disease (CAD) induce atherosclerosis through endothelial activation and dysfunction, and ample evidence now suggests that the balance between production and removal of reactive oxygen species (ROS) - a condition termed oxidative stress - is implicated in such processes. A main source of ROS in vascular cells is the reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase system. This is a membrane-associated enzyme, composed of five subunits, catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the electron donor. One of the system subunits, termed p22-phox, has a polymorphic site on exon 4, associated with variable enzyme activity. This polymorphism is generated by a point mutation (C(242)T) producing a substitution of histidine with tyrosine at position 72, which affects one of the heme binding sites essential for the NAD(P)H enzyme activity. The consequent decrease of superoxide production thus characterizes a phenotype candidate for conferring to the carrier a reduced susceptibility to CAD. At present, however, the body of evidence from current literature is not yet sufficient to confirm or exclude the hypothesis that the C(242)T polymorphism protects from CAD. The functional effects of this polymorphism and the potential and its pathophysiological consequences also need further investigation.
Soccio
M
M
Institute of Cardiology, Center of Excellence on Ageing, G. d'Annunzio University, Chieti, Italy.
Toniato
E
E
Evangelista
V
V
Carluccio
M
M
De Caterina
R
R
D003324:Coronary Artery Disease / Q000209:etiology* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C086986:CYBA protein, human