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Suppression of cholesterol synthesis in cultured fibroblasts from a patient with homozygous familial hypercholesterolemia by her own low density lipoprotein density fraction. A possible role of apolipoprotein E

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Author: Havekes, L. · Vermeer, B.J. · Wit, E. de
Institution: Gaubius instituut TNO
Source:Biochimica et Biophysica Acta, 3, 617, 529-535
Identifier: 228858
Keywords: Biology · Apolipoproteins · Apolipoproteins E · Cells, Cultured · Cholesterol · Female · Fibroblasts · Homozygote · Human · Hypercholesterolemia, Familial · Lipoproteins, LDL · Phospholipids


The suppression of cellular cholesterol synthesis by low density lipoprotein (LDL) from a normal and from a homozygous familial hypercholesterolemic subject was measured on normal fibroblasts and on fibroblasts derived from the same homozygous familial hypercholesterolemic patient. On normal fibroblasts both LDL preparations (density 1.019 to 1.063 g/ml) exerted a similar suppression of cellular cholesterol synthesis. With the homozygous familial hypercholesterolemic fibroblasts homozygous hypercholesterolemic LDL suppressed the cholesterol synthesis to a much greater extent than did LDL from a normal subject. Analysis of lipid and protein composition of both LDL preparations showed that homozygous hypercholesterolemic LDL differs from normal LDL. In the homozygous hypercholesterolemic LDL preparation the ratio phosphatidylcholine to sphingomyelin is decreased, and even when taking a narrower density range (1.023 to 1.045 g/ml), apolipoprotein E is present. In this homozygous hypercholesterolemic LDL preparation (density range 1.023 to 1.045 g/ml) apoliprotein E could be present as an integral LDL protein constituent or as an apolipoprotein) of an HDL(c)-like lipoprotein class with a floatation density similar to that of LDL. It is suggested that the presence of apolipoprotein) E in the LDL density fraction from plasma from this homozygous familial hypercholesterolemic patient could offer an additional means for suppression of cellular cholesterol synthesis of this patient. Chemicals/CAS: cholesterol, 57-88-5; Apolipoproteins E; Apolipoproteins; Cholesterol, 57-88-5; Lipoproteins, LDL; Phospholipids