SPECIFIC REDUCTION OF PLASMA LARGE, LIGHT LOW-DENSITY-LIPOPROTEIN BY A BILE-ACID SEQUESTERING RESIN, CHOLEBINE (MCI-196) IN TYPE-II HYPERLIPOPROTEINEMIA

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)-rece ptor 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 subfract ions. Twelve weeks of treatment with cholebine reduced plasma levels o f total cholesterol (TC) and LDL-cholesterol (C) by 8.3 +/- 8.1% (mean +/- S.D.) and 14.3 +/- 11.9%, respectively (P < 0.001), but did not a ffect plasma levels of high density lipoprotein (HDL)-C. Cholebine sig nificantly 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 de nsity lipoprotein (VLDL)-C, intermediate density lipoprotein (IDL)-C, LDL2-C (1.045 < d < 1.063), HDL2-C, and HDL3-C (d > 1.125). Gradient p olyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduc ed 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), respe ctively. Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activitie s. We conclude that cholebine only reduces plasma levels of large, lig ht LDL. This may be due to the stimulation of hepatic LDL-receptor act ivity. (C) 1997 Elsevier Science Ireland Ltd.