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Effects of lovastatin therapy on LDL receptor activity in circulating monocytes and on structure and composition of plasma lipoproteins

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      Abstract

      The effect of lovastatin therapy on LDL-receptor activity in fresh monocytes and on the structure and composition of lipoproteins was determined in 9 patients with familial hypercholesterolemia (FH) and 8 patients with non-familial hypercholesterolemia (NFH). Lovastatin reduced LDL-cholesterol levels by 34.8 and 47.5%, respectively, in the 2 groups of patients, and plasma apo B levels by 33.3 and 42.5%. LDL receptor activity in fresh monocytes increased by 53% and 86% respectively. HDL-cholesterol and plasma apo A-I levels increased only in the NFH group, by 10.2 and 7.1%. Lipoproteins were separated by centrifugation on a zonal rotor. Except for the intermediate density lipoprotein (IDL) fraction, no changes were observed in the structure and composition of the various lipoproteins. The investigations thus demonstrated that lovastatin therapy is associated with a measurable and significant increase of LDL-receptor activity in circulating monocytes that may contribute to the lipid lowering action of the drug.

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      References

        • Grundy S.M.
        HMG-CoA reductase inhibitors for treatment of hypercholesterolemia.
        New Engl. J. Med. 1988; 319: 24
        • Henwood J.M.
        • Heel R.C.
        Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidemia.
        Drugs. 1988; 36: 429
        • Tobert J.A.
        • Bell G.D.
        • Birtwell J.
        • James L
        • Kakovetz W.R.
        • Pryor J.S.
        • Buntinx A.
        • Holmes I.B.
        • Chao Y.S.
        • Bolognese J.A.
        Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in healthy volunteers.
        J. Clin. Invest. 1982; 69: 913
        • Grundy S.M.
        • Vega G.L.
        Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia.
        J. Lipid Res. 1985; 26: 1464
        • Hoeg J.M.
        • Zech L.A.
        • Bailey K.R.
        • Gregg R.E.
        • Lackner K.J.
        • Fojo S.S.
        • Anchores M.A.
        • Bojonovski M.
        • Spreches D.L.
        • Brewer H.B.
        Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia.
        Am. J. Cardiol. 1986; 57: 933
        • The Lovastatin Study Group II
        Therapeutic response to lovastatin (mevinolin) in nonfamilial hypercholesterolemia — a multicenter study.
        JAMA. 1986; 256: 2829
        • Havel R.J.
        • Hunninghake D.B.
        • Illingworth D.R.
        • Lees R.D.
        • Stein E.A.
        • Tobert J.A.
        • Bacon S.R.
        • Bolognese J.A.
        • Frost P.H.
        • Lamkin G.E.
        • Lees A.M.
        • Leon A.S.
        • Gardner K.
        • Johnson G.
        • Mellies M.J.
        • Rhymer P.A.
        • Tun P.
        Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia — a multicenter study.
        Ann. Intern. Med. 1987; 107: 609
        • Bilheimer D.W.
        • Grundy S.M.
        • Brown M.S.
        • Goldstein J.L.
        Mevinolin and colestipol stimulate receptormediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes.
        in: Version 5 Edition. Proc. Natl. Acad. Sci. USA. 780. 1983: 4124
        • Ma P.T.C.
        • Gil G.
        • Sudhof T.C.
        • Bilheimer D.W.
        • Goldstein J.L.
        • Brown M.S.
        Mevinolin an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.
        in: Version 5 Edition. Proc. Natl. Acad. Sci. USA. 83. 1986: 8370
        • Brown M.S.
        • Goldstein J.L.
        Lipoprotein receptors in the liver — control signals for plasma cholesterol traffic.
        J. Clin. Invest. 1983; 72: 743
        • Brown M.S.
        • Goldstein J.L.
        A receptor-mediated pathway for cholesterol homeostasis.
        Science. 1986; 232: 34
        • Patsch J.R.
        • Sailer S.
        • Kostner G.
        • Braunsteiner H.
        Separation of the main lipoprotein density classes from human plasma by rate-zonal centrifugation.
        J. Lipid Res. 1974; 15: 356
        • Eisenberg S.
        • Gavish D.
        • Oschry Y.
        • Fainaru M.
        • Deckelbaum R.F.
        Abnormalities in very low, low, and high density lipoproteins in hypertriglyceridemia — reversal toward normal with bezafibrate treatment.
        J. Clin. Invest. 1984; 74: 470
        • Eisenberg S.
        • Oschry Y.
        • Zimmerman J.
        Intravascular metabolism of the cholesteryl ester moiety of rat plasma lipoproteins.
        J. Lipid Res. 1984; 25: 121
        • Friedewald W.
        • 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
        • Slutzky G.M.
        • Inbar M.
        • Eisenberg S.
        Quantitative determination of apolipoproteins AI and B with a rapid immunoturbidometric assay.
        Clin. Chem. 1987; 33: 897
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265
        • Bartlett G.R.
        Phosphorus assay in column chromatography.
        J. Biol. Chem. 1959; 234: 466
        • Patsch W.
        • Sailer S.
        • Braunsteiner H.
        An enzymatic method for the determination of the initial rate of cholesterol esterification in human plasma.
        J. Lipid Res. 1976; 17: 182
        • Boyum A.
        Isolation of leucocytes from human blood - further observations.
        Scand. J. Clin. Lab. Invest. 1968; 21: 31
        • Mistry P.
        • Miller N.E.
        • Laker M.
        • Hazzard W.R.
        • Lewis B.
        Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular cholesterol homeostasis in man.
        J. Clin. Invest. 1981; 67: 493
        • Kleinman Y.
        • Eisenberg S.
        • Oschry Y.
        • Gavish D.
        • Stein O.
        • Stein Y.
        Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts — normalization with bezafibrate therapy.
        J. Clin. Invest. 1985; 75: 1796
      1. Siegel S. Nonparametric Statistics. McGraw Hill, Kogakasha Ltd, Tokyo1955
        • Hagemenas F.C.
        • Illingworth D.R.
        Cholesterol homeostasis in-mononuclear leucocytes from patients with familial hypercholesterolemia treated with lovastatin.
        Arteriosclerosis. 1989; 9: 355
        • Chait A.
        • Henze K.
        • Mazzone T.
        • Jensen M.
        • Hammond W.
        Low density lipoprotein receptor activity in freshly isolated human blood monocytes and lymphocytes.
        Metabolism. 1982; 31: 721
        • Thiery J.
        • Armstrong V.W.
        • Schleef J.
        • Creutzfeldt C.
        • Creutzfeldt W.
        • Seidel D.
        Serum lipoprotein Lp(a) concentrations are not influenced by an HMG CoA reductase inhibitor.
        Klin. Wochenschr. 1988; 66: 462
        • Gavish D.
        • Oschry Y.
        • Fainaru M.
        • Eisenberg S.
        Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy — studies in type IIA and type IIB hyperhpoproteinaemia.
        Eur. J. Clin. Invest. 1986; 16: 61