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

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• 作者：Lorenzo Loffredo ; MD¹ ; ^{lorenzo.loffredo@uniroma1.it} ; Francesco Martino ; MD² ; Roberto Carnevale ; PhD¹ ; Pasquale Pignatelli ; MD¹ ; Elisa Catasca ; MD¹ ; Ludovica Perri ; MD¹ ; Cinzia M. Calabrese ; MD¹ ; Maria Michela Palumbo ; MD¹ ; Francesco Baratta ; MD¹ ; Maria Del Ben ; MD¹ ; Francesco Angelico ; MD¹ ; Francesco Violi ; MD¹
• 关键词：BMI ; Body mass index ; 8-iso-PGF2¦Á ; Isoprostanes ; FMD ; Flow-mediated arterial dilation ; HC ; Children with hypercholesterolemia ; HOC ; Children with coexistence of hypercholesterolemia and obesity ; HS ; Healthy subjects ; IMT ; Intima media thickness ; LDL ; Low
• 刊名：The Journal of Pediatrics
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：161
• 期：6
• 页码：1004-1009
• 全文大小：291 K

文摘

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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.

Study design

We performed a cross-sectional study comparing flow-mediated arterial dilation (FMD), oxidized low-density lipoprotein, and urinary excretion of isoprostanes (8-iso-PGF2¦Á), 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-PGF2¦Á 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 (¦Â: ?0.585; P < .001; R² = 35 % ) and sNOX2-dp (¦Â: 0.587; P < .001; R² = 34 % ).

Conclusion

The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.