Promotion of sterol efflux and net transport by apolipoprotein E in lecithin:cholesterol acyltransferase deficiency.
In the plasma of 4 subjects homozygous for deficiency of lecithin:cholesterol acyltransferase, the level of many apolipoproteins (apo A-I, apo A-II, apo B, apo D) was greatly relative to normal, while that of apo E is increased 5-fold. The lipoprotein complex containing lecithin:cholesterol acyltransferase with apo A-I and apo D in normal plasma is completely absent. The major part of apo E is unassociated with other apolipoproteins. The apoprotein-dependence of sterol efflux and net transport from human skin fibroblasts into plasma was determined by immunoaffinity chromatography. In normal plasma the major component of efflux of sterol radioactivity from labeled fibroblasts was dependent upon unassociated apo A-I. In LCAT-deficient plasma, apoprotein-dependent efflux was largely a function of unassociated apo E. When fibroblasts were incubated with fibrinogen-free unfractionated LCAT-deficient plasma, there was no spontaneous net transport of sterol either into or from the cells, indicating that efflux and influx rates were in balance. When apo E was removed by affinity chromatography, there was net transport from plasma to cells. These findings suggest a novel metabolic role for apo E in the promotion of sterol transport uncoupled to LCAT-activity.
D001053:Apolipoproteins / Q000097:blood*; D001057:Apolipoproteins E; D001692:Biological Transport; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007009:Hypolipoproteinemias / Q000097:blood*; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood*; D013261:Sterols / Q000097:blood*
D001053:Apolipoproteins; D001057:Apolipoproteins E; D013261:Sterols