The binding of very low density lipoprotein remnants to the low density lipoprotein receptor in familial defective apolipoprotein B-100

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      We have compared the affinity for low density lipoprotein (LDL) receptors of LDL and very low density lipoprotein (VLDL) remnants from patients with familial defective apo B-100 (FDB) with that of LDL and VLDL remnants from normal subjects. The binding affinity of FDB LDL was markedly reduced in all 14 FDB patients examined, but the affinity of FDB remnants did not differ significantly from that of remnants prepared from normal subjects. Since the mutant form of apo B-100 present in FDB is recognized by LDL receptors with greatly reduced efficiency, we suggest that apo B plays only a minor role in the receptor-mediated uptake of VLDL remnants by the liver in man. These results are consistent with our previous suggestion that the ability of drugs that stimulate hepatic receptor activity to lower the plasma LDL level in FDB is due in part to increased hepatic uptake of lipoprotein precursors of LDL, including remnant particles with normal apo B-100 and those with mutant apo B-100.


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        • Soria L.F.
        • Ludwig E.H.
        • Clarke H.R.G.
        • Vega G.L.
        • Grundy S.M.
        • McCarthy B.J.
        Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.
        in: 2nd Edn. Proc. Natl Acad. Sci. USA.86. 1989: 587
        • Innerarity T.L.
        • Balestra M.E.
        • Arnold K.S.
        • Mahley R.M.
        • Vega G.L.
        • Grundy S.M.
        • Young S.G.
        Isolation of defective receptor-binding low-density lipoproteins from subjects with familial defective apolipoprotein B-100.
        Arteriosclerosis. 1988; 8: 551a
        • Schuster H.
        • Rauh G.
        • Kormann B.
        • et al.
        Familial defective apolipoprotein B-100. Comparison with familial hypercholesterolemia in 18 cases detected in Munich.
        Arteriosclerosis. 1990; 10: 577
        • Myant N.B.
        • Gallagher J.J.
        • Knight B.L.
        • et al.
        Clinical signs of familial hypercholesterolemia in patients with familial defective apolipoprotein B-100 and normal low-density lipoprotein receptor function.
        Arterioscler. Thromb. 1991; 11: 691
        • Tyjbærg-Hansen A.
        • Humphries S.E.
        Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease.
        Atherosclerosis. 1992; 96: 91
        • Maher V.M.G.
        • Gallagher J.J.
        • Thompson G.R.
        • Myant N.B.
        Response to cholesterol-lowering drugs in familial defective apolipoprotein B-100.
        Atherosclerosis. 1991; 91: 73
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499
        • Tybærg-Hansen A.
        • Gallagher J.
        • Vincent J.
        • Talmud P.
        • Dunning A.M.
        • Seed M.
        • Hamsten A.
        • Humphries S.E.
        • Myant N.B.
        Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.
        Atherosclerosis. 1990; 80: 235
        • Lowry O.H.
        • Roseborough N.J.
        • Farr N.J.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265
        • Osborne J.C.
        Delipidation of plasma lipoproteins.
        Methods Enzymol. 1986; 128: 213
        • Kane J.P.
        • Sata T.
        • Hamilton R.L.
        • Havel R.J.
        Apoprotein composition of very low density lipoproteins of human serum.
        J. Clin. Invest. 1975; 56: 1622
        • Turner P.R.
        • Miller N.E.
        • Cortese C.
        • Hazzard W.
        • Coltart J.
        • Lewis B.
        Splanchnic metabolism of plasma apolipoprotein B.
        J. Clin. Invest. 1981; 67: 1678
        • Gallagher J.J.
        • Myant N.B.
        Does the EcoRI polymorphism in the human apolipoprotein B gene affect the binding of low density lipoprotein to the low density lipoprotein receptor?.
        Arteriosclerosis. 1992; 12: 256
        • Bilheimer D.W.
        • Goldstein J.L.
        • Grundy S.M.
        • Brown M.S.
        Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia.
        J. Clin. Invest. 1975; 56: 1420
        • Goldstein J.L.
        • Basu S.K.
        • Brown M.S.
        Receptor-mediated endocytosis of low-density lipoprotein in cultured cells.
        Methods Enzymol. 1983; 98: 241
        • Innerarity T.L.
        • Weisgraber K.H.
        • Arnold K.S.
        • et al.
        Familial defective apolipoprotein B-100. Low density lipoproteins with abnormal receptor binding.
        in: 2nd Edn. Proc. Natl Acad. Sci. USA.84. 1987: 6919
        • Myant N.B.
        Cholesterol Metabolism, LDL, and the LDL Receptor.
        Academic Press Inc, San Diego, CA1990 (Chap. 7)
        • Grundy S.M.
        Multifactorial etiology of hypercholesterolemia. Implications for prevention of coronary heart disease.
        Arteriosclerosis. 1991; 11: 1619
        • Vega G.L.
        • Krauss R.M.
        • Grundy S.M.
        Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B-containing lipoproteins.
        J. Int. Med. 1990; 227: 81
        • Soutar A.K.
        • Myant N.B.
        • Thompson G.R.
        The metabolism of very low density and intermediate density lipoproteins in patients with familial hypercholesterolaemia.
        Atherosclerosis. 1982; 43: 217
        • Kita T.
        • Brown M.S.
        • Bilheimer D.W.
        • Goldstein J.L.
        Delayed clearance of very low density and intermediate density lipoproteins with enhanced conversion to low density lipoprotein in WHHL rabbits.
        in: 2nd Edn. Proc. Natl Acad. Sci. USA.79. 1982: 5693
        • Havel R.J.
        The formation of LDL: mechanisms and regulation.
        J. Lipid Res. 1984; 25: 1570
        • Hui D.Y.
        • Innerarity T.L.
        • Milne R.W.
        • Marcel Y.L.
        • Mahley R.W.
        Binding of chylomicron remnants and beta-very-low-density lipoproteins to hepatic and extrahepatic lipoprotein receptors: a process independent of apolipoprotein B48.
        J. Biol. Chem. 1984; 259: 15060
        • Arbeeny C.M.
        • Rifici V.A.
        • Handley D.A.
        • Eder H.A.
        Determinants of the uptake of very low density lipoprotein remnants by the perfused rat liver.
        Metabolism. 1987; 36: 1106
        • Mahley R.W.
        • Innerarity T.L.
        Lipoprotein receptors and cholesterol homeostasis.
        Biochim. Biophys. Acta. 1983; 737: 197
        • Friedman G.
        • Gavish D.
        • Vogel T.
        • Eisenberg S.
        Cellular metabolism of human plasma intermediate-density lipoprotein (IDL).
        Biochim. Biophys. Acta. 1990; 1044: 118