Plasma-soluble CD40 is related to cholesterol metabolism in patients with moderate hypercholesterolemia

Scand Cardiovasc J. 2006 Oct;40(5):280-4. doi: 10.1080/14017430600959978.

Abstract

Objectives: 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.

Design: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology
  • Atorvastatin
  • Biomarkers / blood
  • CD40 Antigens / blood*
  • Cholesterol / blood*
  • Cholesterol / metabolism*
  • Cholesterol / pharmacology
  • Cholesterol, Dietary / blood
  • Cholesterol, Dietary / metabolism
  • Female
  • Heptanoic Acids / pharmacology
  • Humans
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / metabolism*
  • Male
  • Pyrroles / pharmacology
  • Severity of Illness Index
  • Simvastatin / pharmacology
  • Solubility

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • CD40 Antigens
  • Cholesterol, Dietary
  • Heptanoic Acids
  • Pyrroles
  • lathosterol
  • Cholesterol
  • Atorvastatin
  • Simvastatin