© 1998 American Heart Association, Inc.
Original Contributions |
Sterol 27-Hydroxylase– and ApoAI/Phospholipid–Mediated Efflux of Cholesterol From Cholesterol-Laden Macrophages
Evidence for an Inverse Relation Between the Two Mechanisms
From King Gustaf V Research Institute, Karolinska Hospital, Stockholm (J.W., B.K., J.N.); and Department of Medical Laboratory Science and Technology, Division of Clinical Chemistry, Karolinska Institute, Huddinge (I.B., U.D.), Sweden.
Correspondence to Jan Westman, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden.
Abstract—Cholesterol-laden, human monocyte–derived macrophages were found to contain 27-hydroxycholesterol in proportion to their content of cholesterol ester. In accordance with previous work with human lung alveolar macrophages, there was a significant efflux of 27-hydroxycholesterol and 3ß-hydroxy-5-cholestenoic acid from the cultured cells. The efflux of 27-hydroxycholesterol was proportional to the cellular content of this steroid. Incubation of cholesterol-laden macrophages with reconstituted discoidal complexes made from apolipoprotein A-I and phospholipids resulted in a decrease in total cellular cholesterol, an increase in the efflux of free cholesterol, and a concomitant decrease in the total production and efflux of 27-oxygenated steroids, in particular, 3ß-hydroxy-5-cholestenoic acid. Reconstituted discoidal complexes with the Milano variant of apolipoprotein A-I gave virtually identical results, whereas high density lipoprotein was less efficient. These results suggest that cultured cholesterol-laden cells can export some of their excess cholesterol in the form of 27-hydroxycholesterol, 3ß-hydroxy-5-cholestenoic acid, and free cholesterol. In the presence of exogenous cholesterol acceptors, export of free cholesterol becomes more effective, resulting in less cholesterol exported via the 27-hydroxylase pathway. The balance between the two mechanisms for removal of cholesterol from macrophages may be of importance for formation of foam cells and development of atherosclerosis.
Key Words: foam cell macrophages • 27-hydroxylase • 27-oxygenated sterols • HDL • cholesterol acceptor
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