title: Apolipoprotein E accelerates the efflux of cholesterol from macrophages: mechanism of xanthoma formation in apolipoprotein E deficiency.
abstract: A patient with congenitally deficient apolipoprotein (apo) E showed numerous tuberoerutive, tendon xanthomas and severe atherosclerosis, despite a low LDL concentration. In order to study the mechanism of xanthoma formation observed in apo E deficient patients, we evaluated the effect of VLDL and HDL from the patient on cholesterol ester (CE) accumulation in macrophages. The results showed that there was no difference in CE formation in macrophages among normal VLDL, the patient's VLDL and apo E containing VLDL, which was prepared by incubation of the patient's VLDL with recombinant apo E. On the other hand, apo E containing HDL, which was prepared by incubation of the patient's HDL with recombinant apo E, accelerated cholesterol efflux more effectively than did the patient's HDL and decreased intracellular CE content. Moreover, free apo E accelerated cholesterol efflux from lipid loaded macrophages. These results suggest that macrophages are prevented from transforming into foam cells by their secretion of apo E. This may also explain the marked atherosclerosis and xanthomatosis observed in the patient with apo E-deficiency.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kinoshita
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimaki
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Teramoto
mesh_terms: D001057:Apolipoproteins E / Q000172:deficiency*; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D014973:Xanthomatosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D002784:Cholesterol