title: Early increase of oxidative stress and soluble CD40L in children with hypercholesterolemia.
abstract: OBJECTIVE
  The aim of the study was to analyze the behavior of oxidative stress and its interplay with CD40L, a protein that is implicated in atherosclerosis, in hypercholesterolemic children.
  
  
  BACKGROUND
  Oxidative stress has been suggested to play a major role in premature atherosclerosis.
  
  
  METHODS
  Forty-one children with hypercholesterolemia (mean age 9.28 +/- 0.5 years) and 40 children with normocholesterolemia (mean age 9.02 +/- 0.69 years) were matched for gender and age. Within each group, children were classified as having or not having a family history of cardiovascular disease. Serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, and plasma levels of soluble CD40L (sCD40L) were measured in each child. In a subgroup of children with high (n = 8) or normal (n = 8) levels of serum cholesterol, platelet p38 mitogen-activated protein (MAP) kinase phosphorylation, a protein involved in the activation of nicotinamide adenine dinucleotide phosphate oxidase, was determined.
  
  
  RESULTS
  Children with hypercholesterolemia had higher values of 8-OHdG and sCD40L compared with control subjects (0.55 +/- 0.06 ng/ml vs. 0.21 +/- 0.02 ng/ml, p < 0.001 and 0.55 +/- 0.04 ng/ml vs. 0.19 +/- 0.03 ng/ml, p < 0.001, respectively). A significant correlation between 8-OHdG and sCD40L was observed in children with high (r = 0.676, p < 0.001) or normal (r = 0.878, p < 0.001) levels of cholesterol. Children with a family history of cardiovascular disease tended to have higher values of 8-OHdG and sCD40L, but the difference was not significant. Analysis of platelet p38 MAP kinase showed that it was phosphorylated more in children with hypercholesterolemia compared with control subjects (36.8 +/- 5.8 AU vs. 8.0 +/- 4.5 AU, p < 0.001 respectively).
  
  
  CONCLUSIONS
  Children with hypercholesterolemia have an early increase of oxidative stress that may be responsible for up-regulation of CD40L and potentially predispose to premature atherosclerosis.
authors.affiliation: Center of Clinic Lipid Research, Department of Pediatrics, University of Rome La Sapienza, Rome, Italy. francesco.violi@uniroma1.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Martino
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Eliana
authors.initials: E
authors.lastname: Martino
authors.forename: Francesco
authors.initials: F
authors.lastname: Morrone
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Serena
authors.initials: S
authors.lastname: Di Santo
authors.forename: Barbara
authors.initials: B
authors.lastname: Buchetti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001792:Blood Platelets / Q000502:physiology; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D023201:CD40 Ligand; D000080242:8-Hydroxy-2'-Deoxyguanosine; D048051:p38 Mitogen-Activated Protein Kinases; D003849:Deoxyguanosine