Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:208-212
© 1996 American Heart Association, Inc.
Articles |
Importance of a Novel Oxidative Mechanism for Elimination of Intracellular Cholesterol in Humans
From the Department of Medical Laboratory Sciences and Technology (E.L., A.B., G.A., U.D., I.B.), Department of Lung Medicine (O.A.), and Department of Internal Medicine (K.E.), Karolinska Institute, Huddinge Hospital (Sweden), and the Department of Medical Biochemistry and Biophysics (J.Z., J.S.), Karolinska Institute, Stockholm, Sweden.
Correspondence to Dr Ingemar Björkhem, Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
Abstract We have recently demonstrated that cultured
human alveolar macrophages efficiently convert
cholesterol into excretable 27-oxygenated
products. We show here that increasing the intracellular
concentration of cholesterol by a factor of 10 leads to
about a twofold increase in the excretion of 27-oxygenated
products from cultured macrophages. Inhibition of the
sterol 27-hydroxylase caused a significant intracellular accumulation
of cholesterol. A direct comparison was made between flux
of cholesterol and 27-oxygenated
products from macrophages preloaded with
[4-14C]cholesterol. Under the specific
conditions employed with fetal calf serum in the culture medium, the
flux of 27-oxygenated products was about 10% of that
of cholesterol. Since the sterol 27-hydroxylase, which
converts cholesterol to 27-oxygenated
products, is present in many cell types, we suggest that
27-oxygenation is a general mechanism for removal of
intracellular cholesterol. To evaluate this hypothesis, we
measured the net uptake by the human liver of circulating
27-oxygenated products, which was found to be about 20
mg/24 h. This uptake corresponds to 
4% of the bile acid
production, assuming quantitative conversion into bile acids.
It is concluded that the 27-hydroxylase pathway is of significance for
elimination of extrahepatic cholesterol.
Key Words: sterol 27-hydroxylase • atherosclerosis • macrophages • bile acid biosynthesis • cholesterol degradation
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