title: Plasma-soluble CD40 is related to cholesterol metabolism in patients with moderate hypercholesterolemia.
abstract: OBJECTIVE
  CD40 is a marker of immunological activation and is expressed in the atherosclerotic lesions. We studied whether CD40 and cholesterol synthesis pathways are associated with each other.
  
  
  METHODS
  Forty-three subjects were randomly assigned to receive either simvastatin (n = 14), atorvastatin (n = 15), or placebo (n = 14) for eight weeks. Plasma samples were obtained before and at the end of the follow-up. sCD40 levels were measured in duplicate using an enzyme-linked immunosorbent assay. Cholesterol, its precursor lathosterol, the plant sterols campesterol and sitosterol as well as 27-hydroxycholesterol were quantified by gas-liquid chromatography-mass spectrometry.
  
  
  RESULTS
  sCD40 was inversely correlated with the lathosterol to cholesterol ratio (r = - 0.47, p = 0.002), an indicator of cholesterol synthesis rate, as well as apolipoprotein A-I (r = - 0.38, p = 0.01) in addition to being directly correlated with 27-hydroxycholesterol (r = 0.40, p = 0.008). In multivariate linear regression analysis these three predictors explained 37% of the total variability of sCD40 levels. Simvastatin or atorvastatin treatment had no significant effect on sCD40 levels.
  
  
  CONCLUSIONS
  These results indirectly suggest that sCD40 concentrations are related to cellular cholesterol levels. This may be a novel indication for the relationship between immunological processes and cholesterol metabolism.
authors.affiliation: Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Department of Clinical Chemistry, Tampere and Medical School, Tampere University HospitalUniversity of Tampere, P.O. Box 2000, FI-33521, Finland. mari.luomala@uta.fi
authors.forename: Mari
authors.initials: M
authors.lastname: Luomala
authors.forename: Hannu
authors.initials: H
authors.lastname: Päivä
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Karin
authors.initials: K
authors.lastname: Thelen
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Nina
authors.initials: N
authors.lastname: Peltonen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D019013:CD40 Antigens / Q000097:blood*; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism* / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000097:blood / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D011758:Pyrroles / Q000494:pharmacology; D012720:Severity of Illness Index; D019821:Simvastatin / Q000494:pharmacology; D012995:Solubility
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D019013:CD40 Antigens; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D011758:Pyrroles; C001521:lathosterol; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin