Effect of pravastatin on metabolic parameters of apolipoprotein B in patients with mixed hyperlipoproteinemia |
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Authors: | K G Parhofer P H R Barrett J Dunn G Schonfeld |
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Institution: | (1) Division of Atherosclerosis and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis;(2) Medizinische Klinik II, Klinikum Großhadern, Ludwig-Maximilians-Universität München, Germany;(3) Resource Facility for Kinetic Analysis, Center for Bioengineering, University of Washington, Seattle;(4) Medizinische Klinik II Klinikum Großhadern, Marchionnistrasse 15, D-81366 München, Germany |
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Abstract: | Summary 3-Hydroxy-3-methylgluratyl coenzyme A reductase inhibitors reduce plasma cholesterol in different forms of hyperlipoproteinemia. Although an increase in low-density lipoprotein (LDL) receptor activity is the proven mechanism of this therapy in familial hypercholesterolemia, the mechanism remains controversial in mixed hyperlipoproteinemia. A decreased production of apolipoprotein B (apoB) and/or an increased removal of lipoproteins could mediate the hypocholesterolemic effect of these drugs. The effect of pravastatin on the metabolism of apoB was evaluated in a randomized, double blind, placebo controlled, cross-over study in five men with mixed hyperlipoproteinemia. Metabolic parameters for apoB were determined using endogenous labeling with 1t3C]leucine and 15N]glycine and multicompartmental modeling. During pravastatin therapy cholesterol, LDL cholesterol, apoB, and LDL apoB levels were significantly reduced (P < 0.01) by 18%, 20%, 27%, and 29%, respectively, while triglyceride and high-density lipoprotein cholesterol levels remained unchanged. Pravastatin therapy increased the fractional catabolic rate of very low density lipoprotein apoB from 3.9±0.6 to 5.1±1.7 per day (P = 0.08) and that of LDL apoB from 0.37±0.09 to 0.46±0.10 per day (P<0.01). The apoB production (placebo 35.2±11.9 mg/kg per day; pravastatin 25.8±8.7 mg/kg per day) and conversion of very low density lipoprotein apoB to LDL apoB (placebo 65%, pravastatin 57%) remained stable. Thus, also in mixed hyperlipoproteinemia 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the catabolism of apoB-containing lipoproteins without significantly affecting the production of apoB.Abbreviations apoB
apolipoprotein B
- FCR
fractional catabolic rate
- HMG
hydroxy-methylglutaryl
- CoA
coenzyme A
- FH
familial hypercholesterolemia
- HDL
high-density lipoprotein
- IDL
intermediate-density lipoprotein
- LDL
low-density lipoprotein
- VLDL
very low density lipoprotein
Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday |
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Keywords: | Lipoprotein metabolism Hyperlipoproteinemia Kinetics Pravastatin |
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