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Published on: October 15, 2010
Osteopontin is BMI-independently Related to Early Endothelial Dysfunction in Children
Moritz Schreier1, Julian Tristan Schwartze1, Kathrin Landgraf1
1Center for Pediatric Research Leipzig, Hospital for Children & Adolescents (M.S., J.T.S., K.L., K.S., W.K., A.K.), University of Leipzig, 04103 Leipzig, Germany; Integrated Research and Treatment Center (IFB) Adiposity Diseases (K.L., A.K.), University of Leipzig, 04103 Leipzig, Germany; Heart Centre, Department of Cardiology (S.E.), University of Leipzig, 04109 Leipzig, Germany; Department of Environmental Immunology (G.H.), UFZ Helmholtz Centre for Environmental Research Leipzig, 04318 Leipzig, Germany; Max Planck Institute of Immunology and Epigenetics (J.A.P.), 79108 Freiburg, Germany; and Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (J.K.), University of Leipzig, 04109 Leipzig, Germany.
Insights
Osteopontin (OPN) levels in children are linked to early endothelial dysfunction, independent of body mass index (BMI). This suggests OPN may be an early marker for cardiovascular issues in pediatric obesity.
Area of Science:
- Pediatric Endocrinology
- Cardiovascular Research
- Metabolic Syndrome
Background:
- Osteopontin (OPN) is implicated in adverse cardiac events in adults with type 2 diabetes.
- The role of OPN in pediatric obesity and early cardiovascular dysfunction requires further investigation.
Purpose of the Study:
- To investigate associations of circulating OPN and adipose tissue OPN expression with obesity in children.
- To assess the relationship between OPN and early metabolic and cardiovascular dysfunction.
- To evaluate the functional relevance of OPN on human endothelial cells.
Main Methods:
- Serum OPN measured by ELISA in lean and obese children.
- OPN expression in subcutaneous adipose tissue (AT) assessed by qRT-PCR.
- Direct effects of recombinant OPN on endothelial cells evaluated.
Main Results:
- Serum OPN decreased with puberty in lean children and was negatively associated with obesity.
- OPN levels correlated with markers of endothelial dysfunction (VCAM-1, intima media thickening) independently of BMI.
- Adipose tissue OPN expression correlated with BMI, inflammation, and metabolic dysfunction markers.
Conclusions:
- Circulating OPN levels are independently associated with early endothelial dysfunction markers in children.
- OPN may serve as a potential biomarker for subclinical cardiovascular changes in pediatric obesity.
Context:
Osteopontin (OPN) has been proposed to predict adverse cardiac events in patients with adult type 2 diabetes.
Objective:
We investigated potential associations of circulating OPN and OPN expression in adipose tissue (AT) with obesity and early metabolic and cardiovascular dysfunction in children. Furthermore, we assessed the functional relevance of OPN on primary human endothelial cells.
Design:
Serum OPN was determined in healthy lean (n = 65) and obese (n = 100) children by ELISA. Expression levels were assessed in sc AT samples from healthy lean (n = 33) and overweight and obese (n = 31) children by qRT-PCR. Direct effects of recombinant (rh) OPN on adhesion molecule and ENOS expression were assessed in human coronary arterial endothelial cells.
Results:
OPN serum concentrations decreased with pubertal development in lean children. The degree of obesity was negatively associated with OPN serum levels. Multiple regression analysis revealed that body mass index (BMI) standard deviation score (SDS), next to pubertal status, was the strongest independent predictor for OPN serum concentrations. Metabolically, the homeostasis model assessment index and circulating plasma insulin were negatively correlated with OPN serum levels secondary to obesity. In contrast, independent from BMI, OPN was positively related to VCAM-1 levels, intima media thickening, and negatively associated with endothelial function. Functionally, full-length rhOPN did not affect adhesion molecule and ENOS mRNA expression in primary human coronary arterial endothelial cells. In addition, OPN expression levels in AT positively correlated with BMI SDS, AT inflammation, and markers of metabolic dysfunction but were not related to OPN serum levels.
Conclusion:
Our findings suggest that OPN levels are BMI-independently related to markers of early endothelial dysfunction in children.
