Association between Inflammation, Glycocalyx Biomarkers, and Endothelial Function in Children with Hypercholesterolemia

Abstract

<b><i>Introduction:</i></b> Hypercholesterolemia is a risk factor for premature arteriosclerosis. Inflammation and oxidative stress are thought to contribute to endothelial dysfunction preceding vasculopathy. We investigated the association between inflammation, glycocalyx biomarkers, endothelial function, and vascular parameters in children with hypercholesterolemia. <b><i>Methods:</i></b> In 22 patients (LDL-cholesterol &gt;130 mg/dL; median age [IQR]: 13 [2.3] years) and 22 controls (13 [2.5] years), tumor necrosis factor-alpha (TNF-α), oxidized cholesterol (oxLDL), and glycocalyx biomarkers (Syndecan-1, Hyaluronan) were measured using immunoassays. Endothelial function was assessed by peripheral arterial tonometry, sublingual glycocalyx and microcirculation by videomicroscopy and carotid intima-media thickness by ultrasound. <b><i>Results:</i></b> OxLDL was significantly higher in patients (78.9 [38.2] vs. 50.3 [16.6] U/L, <i>p</i> = 0.002), whereas all other experimental parameters were comparable between groups. Multivariate analysis revealed a significant association of Syndecan-1 with TNF-α (β = 0.75, <i>p</i> &lt; 0.001) and with hypercholesterolemia (β = 0.31, <i>p</i> = 0.030). The interaction term combining TNF-α and hypercholesterolemia showed a significant effect (<i>p</i> = 0.034). Sex was an independent predictor of endothelial function. <b><i>Conclusion:</i></b> The combined effect of hypercholesterolemia and inflammation on glycocalyx perturbation and the impact of sex in the premature development of arteriosclerosis deserve further evaluation. Therapeutic approaches tackling low-grade systemic inflammation may offer potential to prevent or delay progression of cardiovascular disease and cardiovascular complications.