Specific reduction of plasma large, light low-density lipoprotein by a bile acid sequestering resin, cholebine (MCI-196) in type II hyperlipoproteinemia. 1997

Y Homma, and T Kobayashi, and H Yamaguchi, and H Ozawa, and H Sakane, and H Nakamura
Department of Internal Medicine, Tokai University, Oiso Hospital, Kanagawa, Japan.

The effect of a bile acid sequestrant, cholebine (3 g/day), on plasma lipoprotein subfractions was investigated in 16 patients with type II hyperlipoproteinemia. Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions. Twelve weeks of treatment with cholebine reduced plasma levels of total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.4 +/- 11.9%, respectively (P < 0.001), but did not affect plasma levels of high density lipoprotein (HDL)-C. Cholebine significantly reduced plasma levels of LDL1-C (1.019 < d < 1.045) by 22.9 +/- 18.9% (P < 0.001) but did not affect plasma levels of very low density lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions. Cholebine did not alter the activities of LCAT and CETP. LDL-receptor activities of cultured lymphocytes negatively correlated with the reduction in plasma levels of LDL-C (r = -0.500, P < 0.05), IDL-C (r = -0.581, P < 0.02), and LDL1-C (r = -0.610, P < 0.01), respectively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities. We conclude that cholebine only reduces plasma levels of large, light LDL. This may be due to the stimulation of hepatic LDL-receptor activity.

UI MeSH Term Description Entries
D007862 Phosphatidylcholine-Sterol O-Acyltransferase An enzyme secreted from the liver into the plasma of many mammalian species. It catalyzes the esterification of the hydroxyl group of lipoprotein cholesterol by the transfer of a fatty acid from the C-2 position of lecithin. In familial lecithin:cholesterol acyltransferase deficiency disease, the absence of the enzyme results in an excess of unesterified cholesterol in plasma. Lecithin Cholesterol Acyltransferase,Cholesterol Ester Lysolecithin Acyltransferase,Lecithin Acyltransferase,Phosophatidylcholine-Sterol Acyltransferase,Acyltransferase, Lecithin,Acyltransferase, Lecithin Cholesterol,Acyltransferase, Phosophatidylcholine-Sterol,Cholesterol Acyltransferase, Lecithin,O-Acyltransferase, Phosphatidylcholine-Sterol,Phosophatidylcholine Sterol Acyltransferase,Phosphatidylcholine Sterol O Acyltransferase
D008074 Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes. Circulating Lipoproteins,Lipoprotein,Lipoproteins, Circulating
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008078 Cholesterol, LDL Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol. LDL Cholesterol,Cholesteryl Linoleate, LDL,LDL Cholesteryl Linoleate,Low Density Lipoprotein Cholesterol,beta-Lipoprotein Cholesterol,Cholesterol, beta-Lipoprotein,beta Lipoprotein Cholesterol
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D006023 Glycoproteins Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins. C-Glycosylated Proteins,Glycosylated Protein,Glycosylated Proteins,N-Glycosylated Proteins,O-Glycosylated Proteins,Glycoprotein,Neoglycoproteins,Protein, Glycosylated,Proteins, C-Glycosylated,Proteins, Glycosylated,Proteins, N-Glycosylated,Proteins, O-Glycosylated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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