Plasma-soluble CD40 is related to cholesterol metabolism in patients with moderate hypercholesterolemia.
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.
Luomala
Mari
M
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
Päivä
Hannu
H
Laaksonen
Reijo
R
Thelen
Karin
K
Lütjohann
Dieter
D
Peltonen
Nina
N
Lehtimäki
Terho
T
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
D000924:Anticholesteremic Agents; D015415:Biomarkers; D019013:CD40 Antigens; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D011758:Pyrroles; C001521:lathosterol; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin