Obesity and Hypercholesterolemia are Associated with NOX2 Generated Oxidative Stress and Arterial Dysfunction

ObjectiveTo analyze the interplay among oxidative stress, NOX2, the catalytic core of nicotinamide-adenine dinucleotide phosphate oxidase, and endothelial dysfunction in children with obesity and/or hypercholesterolemia.Study designWe performed a cross-sectional study comparing flow-mediated arterial dilation (FMD), oxidized low-density lipoprotein, and urinary excretion of isoprostanes (8-iso-PGF2α), as markers of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-dp (sNOX2-dp), in a population of 100 children, matched for age and sex, including 40 healthy subjects (HS), 20 children with hypercholesterolemia (HC), 20 obese children (OC), and 20 children with coexistence of hypercholesterolemia and obesity (HOC).ResultsHOC had higher sNOX2-dp and oxidized low-density lipoprotein levels compared with HS, HC, and OC. HC, OC, and HOC had lower FMD values compared with HS. Urinary 8-iso-PGF2α excretion was higher in HOC compared with HS. FMD was inversely correlated with sNOX2-dp levels (r = −0.483; P < .001) and with the number of cardiovascular risk factors (r = −0.617; P < .001). Multiple linear regression analysis showed that the number of cardiovascular risk factors was the only independent predictive variable associated with FMD (β: −0.585; P < .001; R2 = 35%) and sNOX2-dp (β: 0.587; P < .001; R2 = 34%).ConclusionThe study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.