The characterization of lipoproteins in the high density fraction obtained from patients with familial lecithin:cholesterol acyltransferase deficiency and their interaction with cultured human fibroblasts.
Lipoproteins of density 1.063--1.21 g/ml were isolated from the plasma of three sisters of Irish origin with familial LCAT deficiency. Fractionation of the lipoproteins on the basis of particle size by chromatography on Sephacryl S-300 permitted partial separation of two major and at least three other minor components which differed in their lipid:protein ratio and their apolipoprotein content. One of the major components was a small spherical lipoprotein whose sole apolipoprotein was apoA-I; the second major component contained predominantly apoA-I, together with apoE, and in addition, an apolipoprotein of molecular weight 46,000 that was not cleaved by reduction of disulfide bonds, and which was identified as apoA-IV. This apoprotein has not previously been detected in the lipoproteins of LCAT-deficient patients. A second apoE-containing lipoprotein, which contained apoA-I and apoE in a ratio of approximately 2:1, was also present as a minor component, together with two or more minor components whose apoproteins were comprised of apoA-I and apoC. The apoE-containing lipoproteins competed efficiently with 125I-labeled LDL for binding to high affinity LDL-receptor sites on the surface of cultured human skin fibroblasts. The ability to bind to the LDL-receptor was directly proportional to the apoE content of the lipoproteins, even when other apoproteins, with the exception of apoB, were present in relatively large proportions. ApoE-containing 125I-labeled lipoproteins from an LCAT-deficient subject were also taken up and degraded by the cultured cells.
D001053:Apolipoproteins / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007009:Hypolipoproteinemias / Q000097:blood*; D005779:Immunodiffusion; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D008077:Lipoproteins, LDL / Q000378:metabolism; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL; D012867:Skin / Q000378:metabolism
D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL