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

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.