Whole blood TNF-α expression and apoptotic endothelial microparticles reveal early vascular injury in pediatric obesity.

BACKGROUND

Childhood obesity is increasingly recognized as a trigger for early cardiovascular risk, partly mediated by subclinical inflammation and endothelial dysfunction. This study aimed to evaluate the expression of pro-inflammatory cytokines (TNF-α, IL-17A, and IL-2) in whole blood and investigate their associations with anthropometric measures, blood pressure, microvascular endothelial function, and circulating apoptotic endothelial microparticles (EMPs) in children with healthy weight versus those with overweight/obesity.

METHODS

A cross-sectional study was conducted with 113 children aged 6-11 years, categorized as children with healthy weight (n = 82) or children with overweight/obesity (n = 31) based on BMI-for-age criteria. Endothelial function was assessed using peripheral arterial tonometry by measurement of reactive hyperemia index (RHI) and circulating apoptotic EMPs were measured by flow cytometry. Whole blood mRNA levels of inflammatory cytokines were quantified using qRT-PCR.

RESULTS

Children with overweight/obesity exhibited significantly lower RHI values, indicating early endothelial dysfunction. RHI negatively correlated with BMI (r = -0.485; P < 0.001), waist circumference (r = -0.466; P < 0.001), SBP (r = -0.317, P = 0.001), DBP (r = -0.246; P = 0.009), and LDL-C levels (r = -0.191; P = 0.043). Circulating levels of apoptotic EMPs were elevated in these children and positively associated with adiposity and blood pressure, while inversely correlated with RHI (r = -0.496; P < 0.001). TNF-α expression was significantly upregulated in the overweight/obesity group and correlated positively with BMI (r = 0.468; P = 0.001), waist circumference (r = 0.492; P < 0.001), SBP (r = 0.294; P = 0.040), apoptotic EMPs (r = 0.326; P = 0.022), and negatively with RHI (r = -0.543; P < 0.001). No significant differences were observed for IL-17A or IL-2 expression. The linear regression analysis indicated that high circulating levels of both apoptotic EMPs and TNF-α mRNA were recognized as predictors factors of lower RHI value in the study population.

CONCLUSION

TNF-α gene expression in whole blood and elevated levels of apoptotic endothelial microparticles are closely associated with early endothelial microvascular dysfunction in pediatric obesity. The observed associations underscore the role of inflammation-driven endothelial dysfunction in the pathophysiology of obesity-related cardiovascular risk.