HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arad, Y. Articles by Ginsberg, H. N. Search for Related Content PubMed PubMed Citation Articles by Arad, Y. Articles by Ginsberg, H. N. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 31, 567-582, Copyright © 1990 by Lipid Research, Inc.

ARTICLES

Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production

Y Arad, R Ramakrishnan and HN Ginsberg
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using 125I-labeled VLDL and 131I-labeled LDL and compartmental modeling, before and during lovastatin treatment. Lovastatin therapy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg/dl, P less than 0.0005) and apoB (1328 vs 797 micrograms/ml, P less than 0.001). Before treatment, CHL patients had high production rates (PR) of LDL apoB. Three-fourths of this LDL apoB flux was derived from sources other than circulating VLDL and was, therefore, defined as "cold" LDL apoB flux. Compared to baseline, treatment with lovastatin was associated with a significant reduction in the total rate of entry of apoB-containing lipoproteins into plasma in all seven CHL subjects (40.7 vs. 25.7 mg/kg.day, P less than 0.003). This reduction was associated with a fall in total LDL apoB PR and in "cold" LDL apoB PR in six out of seven CHL subjects. VLDL apoB PR fell in five out of seven CHL subjects. Treatment with lovastatin did not significantly alter VLDL apoB conversion to LDL apoB or LDL apoB fractional catabolic rate (FCR) in CHL patients. In three patients with familial hypercholesterolemia who were studied for comparison, lovastatin treatment increased LDL apoB FCR but did not consistently alter LDL apoB PR. We conclude that lovastatin lowers LDL cholesterol and apoB concentrations in CHL patients by reducing the rate of entry of apoB-containing lipoproteins into plasma, either as VLDL or as directly secreted LDL.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Guerin, W. Le Goff, E. Duchene, Z. Julia, T. Nguyen, T. Thuren, C. L. Shear, and M. J. Chapman Inhibition of CETP by Torcetrapib Attenuates the Atherogenicity of Postprandial TG-Rich Lipoproteins in Type IIB Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 148 - 154. [Abstract] [Full Text] [PDF]

				R. Ramakrishnan Studying apolipoprotein turnover with stable isotope tracers: correct analysis is by modeling enrichments J. Lipid Res., December 1, 2006; 47(12): 2738 - 2753. [Abstract] [Full Text] [PDF]

				K. G. Parhofer and P. H. R. Barrett Thematic review series: Patient-Oriented Research. What we have learned about VLDL and LDL metabolism from human kinetics studies J. Lipid Res., August 1, 2006; 47(8): 1620 - 1630. [Abstract] [Full Text] [PDF]

				H. N. Ginsberg REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 383 - 392. [Abstract] [Full Text] [PDF]

				M. Myerson, C. Ngai, J. Jones, S. Holleran, R. Ramakrishnan, L. Berglund, and H. N. Ginsberg Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia J. Lipid Res., December 1, 2005; 46(12): 2735 - 2744. [Abstract] [Full Text] [PDF]

				J. J. Liang, P. Oelkers, C. Guo, P.-C. Chu, J. L. Dixon, H. N. Ginsberg, and S. L. Sturley Overexpression of Human Diacylglycerol Acyltransferase 1, Acyl-CoA:Cholesterol Acyltransferase 1, or Acyl-CoA:Cholesterol Acyltransferase 2 Stimulates Secretion of Apolipoprotein B-containing Lipoproteins in McA-RH7777 Cells J. Biol. Chem., October 22, 2004; 279(43): 44938 - 44944. [Abstract] [Full Text] [PDF]

				M. Guerin, W. Le Goff, E. Frisdal, S. Schneider, D. Milosavljevic, E. Bruckert, and M. J. Chapman Action of Ciprofibrate in Type IIB Hyperlipoproteinemia: Modulation of the Atherogenic Lipoprotein Phenotype and Stimulation of High-Density Lipoprotein-Mediated Cellular Cholesterol Efflux J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3738 - 3746. [Abstract] [Full Text] [PDF]

				B. H. C. M. T. Prinsen, J. A. Romijn, P. H. Bisschop, M. M. J. de Barse, P. H. R. Barrett, M. Ackermans, R. Berger, T. J. Rabelink, and M. G. M. de Sain-van der Velden Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans J. Lipid Res., July 1, 2003; 44(7): 1341 - 1348. [Abstract] [Full Text] [PDF]

				K. Ouguerram, T. Magot, Y. Zair, J. S. Marchini, B. Charbonnel, H. Laouenan, and M. Krempf Effect of Atorvastatin on Apolipoprotein B100 Containing Lipoprotein Metabolism in Type-2 Diabetes J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 332 - 337. [Abstract] [Full Text] [PDF]

				H. Hiyoshi, M. Yanagimachi, M. Ito, N. Yasuda, T. Okada, H. Ikuta, D. Shinmyo, K. Tanaka, N. Kurusu, I. Yoshida, et al. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes J. Lipid Res., January 1, 2003; 44(1): 128 - 135. [Abstract] [Full Text] [PDF]

				References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]

				M. Guerin, P. Egger, W. Le Goff, C. Soudant, R. Dupuis, and M. J. Chapman Atorvastatin Reduces Postprandial Accumulation and Cholesteryl Ester Transfer Protein-Mediated Remodeling of Triglyceride-Rich Lipoprotein Subspecies in Type IIB Hyperlipidemia J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4991 - 5000. [Abstract] [Full Text] [PDF]

				M. Guerin, P. Egger, C. Soudant, W. Le Goff, A. van Tol, R. Dupuis, and M. J. Chapman Cholesteryl ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hyperlipidemia in the postprandial state J. Lipid Res., October 1, 2002; 43(10): 1652 - 1660. [Abstract] [Full Text] [PDF]

				E. A. Fisher and H. N. Ginsberg Complexity in the Secretory Pathway: The Assembly and Secretion of Apolipoprotein B-containing Lipoproteins J. Biol. Chem., May 10, 2002; 277(20): 17377 - 17380. [Full Text] [PDF]

				D. C. Chan, G. F. Watts, P. H. R. Barrett, T. A. Mori, L. J. Beilin, and T. G. Redgrave Mechanism of Action of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor on Apolipoprotein B-100 Kinetics in Visceral Obesity J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2283 - 2289. [Abstract] [Full Text] [PDF]

				C. Ko, T.-L. Lee, P. W. Lau, J. Li, B. T. Davis, E. Voyiaziakis, D. B. Allison, S. C. Chua , Jr., and L.-S. Huang Two novel quantitative trait loci on mouse chromosomes 6 and 4 independently and synergistically regulate plasma apoB levels J. Lipid Res., May 1, 2001; 42(5): 844 - 855. [Abstract] [Full Text]

				M. Tomas, M. Senti, F. Garcia-Faria, J. Vila, A. Torrents, M. Covas, and J. Marrugat Effect of Simvastatin Therapy on Paraoxonase Activity and Related Lipoproteins in Familial Hypercholesterolemic Patients Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2113 - 2119. [Abstract] [Full Text] [PDF]

				M. Guerin, T. S. Lassel, W. Le Goff, M. Farnier, and M. J. Chapman Action of Atorvastatin in Combined Hyperlipidemia : Preferential Reduction of Cholesteryl Ester Transfer From HDL to VLDL1 Particles Arterioscler. Thromb. Vasc. Biol., January 1, 2000; 20(1): 189 - 197. [Abstract] [Full Text] [PDF]

				J. R. Burnett, L. J. Wilcox, D. E. Telford, S. J. Kleinstiver, P. H. R. Barrett, R. S. Newton, and M. W. Huff The Magnitude of Decrease in Hepatic Very Low Density Lipoprotein Apolipoprotein B Secretion Is Determined by the Extent of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition in Miniature Pigs Endocrinology, November 1, 1999; 140(11): 5293 - 5302. [Abstract] [Full Text]

				R. H. Knopp Drug Treatment of Lipid Disorders N. Engl. J. Med., August 12, 1999; 341(7): 498 - 511. [Full Text] [PDF]

				J. S. Kendrick and J. A. Higgins Dietary fish oils inhibit early events in the assembly of very low density lipoproteins and target apoB for degradation within the rough endoplasmic reticulum of hamster hepatocytes J. Lipid Res., March 1, 1999; 40(3): 504 - 514. [Abstract] [Full Text]

				G. Bittolo-Bon and G. Cazzolato Analytical capillary isotachophoresis of total plasma lipoproteins: a new tool to identify atherogenic low density lipoproteins J. Lipid Res., January 1, 1999; 40(1): 170 - 177. [Abstract] [Full Text]

				H. Jiang, H. N. Ginsberg, and X. Wu Glucose does not stimulate apoprotein B secretion from HepG2 cells because of insufficient stimulation of triglyceride synthesis J. Lipid Res., November 1, 1998; 39(11): 2277 - 2285. [Abstract] [Full Text]

				A. Mohammadi, J. Macri, R. Newton, T. Romain, D. Dulay, and K. Adeli Effects of Atorvastatin on the Intracellular Stability and Secretion of Apolipoprotein B in HepG2 Cells Arterioscler. Thromb. Vasc. Biol., May 1, 1998; 18(5): 783 - 793. [Abstract] [Full Text] [PDF]

				L. Berglund, J. L. Witztum, N. F. Galeano, A. S. Khouw, H. N. Ginsberg, and R. Ramakrishnan Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach J. Lipid Res., April 1, 1998; 39(4): 913 - 924. [Abstract] [Full Text]

				M. Cuchel, E. J. Schaefer, J. S. Millar, P. J.H. Jones, G. G. Dolnikowski, C. Vergani, and A. H. Lichtenstein Lovastatin Decreases De Novo Cholesterol Synthesis and LDL Apo B-100 Production Rates in Combined-Hyperlipidemic Males Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 1910 - 1917. [Abstract] [Full Text]

				C. A. Aguilar-Salinas, P. H. R. Barrett, J. Pulai, X. L. Zhu, G. Schonfeld, and G Schonfeld A Familial Combined Hyperlipidemic Kindred With Impaired Apolipoprotein B Catabolism: Kinetics of Apolipoprotein B During Placebo and Pravastatin Therapy Arterioscler. Thromb. Vasc. Biol., January 1, 1997; 17(1): 72 - 82. [Abstract] [Full Text]

				F. Benoist and T. Grand-Perret ApoB-100 Secretion by HepG2 Cells Is Regulated by the Rate of Triglyceride Biosynthesis but Not by Intracellular Lipid Pools Arterioscler. Thromb. Vasc. Biol., October 1, 1996; 16(10): 1229 - 1235. [Abstract] [Full Text]

				M. Guerin, E. Bruckert, P. J. Dolphin, G. Turpin, and M. J. Chapman Fenofibrate Reduces Plasma Cholesteryl Ester Transfer From HDL to VLDL and Normalizes the Atherogenic, Dense LDL Profile in Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., June 1, 1996; 16(6): 763 - 772. [Abstract] [Full Text]

				X. Wu, M. Zhou, L.-S. Huang, J. Wetterau, and H. N. Ginsberg Demonstration of a Physical Interaction between Microsomal Triglyceride Transfer Protein and Apolipoprotein B during the Assembly of ApoB-containing Lipoproteins J. Biol. Chem., April 26, 1996; 271(17): 10277 - 10281. [Abstract] [Full Text] [PDF]

				J. Hasler-Rapacz, H. J. Kempen, H. M.G. Princen, B. J. Kudchodkar, A. Lacko, and J. Rapacz Effects of Simvastatin on Plasma Lipids and Apolipoproteins in Familial Hypercholesterolemic Swine Arterioscler. Thromb. Vasc. Biol., January 1, 1996; 16(1): 137 - 143. [Abstract] [Full Text]

				G. L. Vega and S. M. Grundy Primary Hypertriglyceridemia With Borderline High Cholesterol and Elevated Apolipoprotein B Concentrations: Comparison of Gemfibrozil vs Lovastatin Therapy JAMA, December 5, 1990; 264(21): 2759 - 2763. [Abstract] [PDF]

				M. Pan, J.-s. Liang, E. A. Fisher, and H. N. Ginsberg Inhibition of Translocation of Nascent Apolipoprotein B across the Endoplasmic Reticulum Membrane Is Associated with Selective Inhibition of the Synthesis of Apolipoprotein B J. Biol. Chem., August 25, 2000; 275(35): 27399 - 27405. [Abstract] [Full Text] [PDF]