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

Christine Prell, Belén Pastor-Villaescusa, Berthold Koletzko, André Jakob, Julia Meier, Fabienne Ruske, Juliane Gruenzner, Miriam Koenig, Claudia Nussbaum

Journal: Annals of nutrition & metabolism 2024;80(5):260-267

PMID: 38316115

Abstract

INTRODUCTION

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.

METHODS

In 22 patients (LDL-cholesterol >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.

RESULTS

OxLDL was significantly higher in patients (78.9 [38.2] vs. 50.3 [16.6] U/L, p = 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, p < 0.001) and with hypercholesterolemia (β = 0.31, p = 0.030). The interaction term combining TNF-α and hypercholesterolemia showed a significant effect (p = 0.034). Sex was an independent predictor of endothelial function.

CONCLUSION

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.

© 2024 S. Karger AG, Basel.

Address: Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Metabolism and Investigation Unit, Reina Sofia University Hospital, Maimonides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Cordoba, Cordoba, Spain.; Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.; Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich, Munich, Germany.
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