Early increase of NOX2-derived oxidative stress in children: relationship with age

BACKGROUND: Studies conducted in the prepubertal period showed that biomarkers of oxidative stress decreased with increasing age in normocholesterolemic children (NC), and, conversely, they are persistently high in hypercholesterolemic children (HC). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the most important cellular source of reactive oxygen species. No data have been reported concerning the behavior of age-related oxidative stress generated by NOX2, the catalytic subunit of NADPH oxidase, in children. METHODS: We performed a cross-sectional study comparing oxidized low-density lipoprotein (ox-LDL), as a marker of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-derived peptide (sNOX2-dp), in a population of 250 children, induding 125 NC and 125 HC. RESULTS: HC had higher sNOX2-dp (25.8 +/- 16.1 pg/ml) and ox-LDL (23.6 +/- 14.4 U/I) levels as compared with NC (15.4 +/- 10.1 and 11.6 +/- 6.4 pg/ml, respectively; P < 0.001). Multiple linear regression analysis showed that ox-LDL and total cholesterol were the only independent predictive variables associated with sNOX2-dp. In NC, ox-LDL and sNOX2-dp significantly decreased from the first to the second quintile of age. In HC, ox-LDL and sNOX2-dp levels did not show significant differences among quintiles of age. CONCLUSION: This study suggests that NOX2 contributes to generating ox-LDL during the early phase of life in NC and to the persistent high oxidative stress in the prepubertal period of HC