Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction.
OBJECTIVE
To 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.


METHODS
We 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).


RESULTS
HOC 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; R(2) = 35%) and sNOX2-dp (β: 0.587; P < .001; R(2) = 34%).


CONCLUSIONS
The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.
I Clinica Medica, Sapienza University, Rome, Italy. lorenzo.loffredo@uniroma1.it
Lorenzo
L
Loffredo
Francesco
F
Martino
Roberto
R
Carnevale
Pasquale
P
Pignatelli
Elisa
E
Catasca
Ludovica
L
Perri
Cinzia M
CM
Calabrese
Maria Michela
MM
Palumbo
Francesco
F
Baratta
Maria
M
Del Ben
Francesco
F
Angelico
Francesco
F
Violi
D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000209:etiology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood*; D009765:Obesity / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D012307:Risk Factors; D014664:Vasodilation
D015415:Biomarkers; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases