title: Osteopontin is BMI-independently Related to Early Endothelial Dysfunction in Children.
abstract: Osteopontin (OPN) has been proposed to predict adverse cardiac events in patients with adult type 2 diabetes.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our findings suggest that OPN levels are BMI-independently related to markers of early endothelial dysfunction in children.
authors: Center 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.
authors: Moritz
authors: M
authors: Schreier
authors: Center 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.
authors: Julian Tristan
authors: JT
authors: Schwartze
authors: Center 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.
authors: Kathrin
authors: K
authors: Landgraf
authors: Center 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.
authors: Kathrin
authors: K
authors: Scheuermann
authors: Center 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.
authors: Sandra
authors: S
authors: Erbs
authors: Center 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.
authors: Gunda
authors: G
authors: Herberth
authors: Center 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.
authors: J Andrew
authors: JA
authors: Pospisilik
authors: Center 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.
authors: Jürgen
authors: J
authors: Kratzsch
authors: Center 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.
authors: Wieland
authors: W
authors: Kiess
authors: Center 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.
authors: Antje
authors: A
authors: Körner
mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D002657:Child Development / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000097:blood*; D050177:Overweight / Q000097:blood*; D063766:Pediatric Obesity / Q000097:blood; D011627:Puberty / Q000097:blood*; D014652:Vascular Diseases / Q000097:blood*
chemical_list: D015415:Biomarkers; C506895:SPP1 protein, human; D053495:Osteopontin