|
 |
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 45, 866-872, May 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation
* Lipid Research Center, CHUL Research Center, Québec, Canada
Institute on Nutraceuticals and Functional Foods, Laval University, Québec, Canada
1 To whom correspondence should be addressed. e-mail: patrick.couture{at}crchul.ulaval.ca
Early radiokinetic studies revealed that the classical metabolic defect in patients with familial hypercholesterolemia (FH) is hypocatabolism of LDL due to decreased LDL receptor activity. However, recent studies have suggested that hepatic oversecretion of apolipoprotein B-100 (apoB-100)-containing lipoproteins could also contribute to the markedly elevated plasma concentrations of LDL-cholesterol found in FH. The aim of this study was to examine the kinetics of apoB-100 labeled with a stable isotope (L-[5,5,5-D3] leucine) in five normolipidemic controls and in seven well-characterized FH subjects that included six FH heterozygotes and one FH homozygote carrying the same null LDL receptor gene mutation. As compared with controls, the VLDL apoB-100 production rate was increased by 50% in the FH heterozygotes and by 109% in the FH homozygote. Furthermore, FH subjects had significantly higher LDL apoB-100 pool size and lower LDL apoB-100 fractional catabolic rate than controls.
These results indicate that the elevation of plasma LDL-cholesterol found in FH is attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipoproteins.
Supplementary key words apolipoprotein B-100 • gas chromatography/mass spectrometry • kinetic
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. A. Blasiole, A. T. Oler, and A. D. Attie Regulation of ApoB Secretion by the Low Density Lipoprotein Receptor Requires Exit from the Endoplasmic Reticulum and Interaction with ApoE or ApoB J. Biol. Chem., April 25, 2008; 283(17): 11374 - 11381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Kolovou, K. K. Anagnostopoulou, D. S. Damaskos, C. Mihas, S. Mavrogeni, G. Hatzigeorgiou, T. Theodoridis, D. P. Mikhailidis, and D. V. Cokkinos Gender Influence on Postprandial Lipemia in Heterozygotes for Familial Hypercholesterolemia Ann. Clin. Lab. Sci., January 1, 2007; 37(4): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Kolovou, G. V.Z. Dedoussis, K. K. Anagnostopoulou, G. Ch. Hatzigeorgiou, K. D. Salpea, D. M. Choumerianou, S. Rammos, D. P. Mikhailidis, and D. V. Cokkinos Management of a Patient With a Null Low-Density Lipoprotein Receptor Mutation: A Case Report Angiology, January 1, 2007; 57(6): 729 - 732. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Lambert, A.-L. Jarnoux, T. Pineau, O. Pape, M. Chetiveaux, C. Laboisse, M. Krempf, and P. Costet Fasting Induces Hyperlipidemia in Mice Overexpressing Proprotein Convertase Subtilisin Kexin Type 9: Lack of Modulation of Very-Low-Density Lipoprotein Hepatic Output by the Low-Density Lipoprotein Receptor Endocrinology, October 1, 2006; 147(10): 4985 - 4995. [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. Duez, B. Lamarche, K. D. Uffelman, R. Valero, J. S. Cohn, and G. F. Lewis Hyperinsulinemia Is Associated With Increased Production Rate of Intestinal Apolipoprotein B-48-Containing Lipoproteins in Humans Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1357 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Tremblay, B. Lamarche, J. S. Cohn, J.-C. Hogue, and P. Couture Effect of Ezetimibe on the In Vivo Kinetics of ApoB-48 and ApoB-100 in Men With Primary Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1101 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lalanne, G. Lambert, M. J. A. Amar, M. Chetiveaux, Y. Zair, A.-L. Jarnoux, K. Ouguerram, J. Friburg, N. G. Seidah, H. B. Brewer Jr., et al. Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells J. Lipid Res., June 1, 2005; 46(6): 1312 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Millar, C. Maugeais, K. Ikewaki, D. M. Kolansky, P.H. R. Barrett, E. C. Budreck, R. C. Boston, N. Tada, S. Mochizuki, J. C. Defesche, et al. Complete Deficiency of the Low-Density Lipoprotein Receptor Is Associated With Increased Apolipoprotein B-100 Production Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 560 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Desroches, M.-E. Paradis, M. Perusse, W. R. Archer, J. Bergeron, P. Couture, N. Bergeron, and B. Lamarche Apolipoprotein A-I, A-II, and VLDL-B-100 metabolism in men: comparison of a low-fat diet and a high-monounsaturated fatty acid diet J. Lipid Res., December 1, 2004; 45(12): 2331 - 2338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Benjannet, D. Rhainds, R. Essalmani, J. Mayne, L. Wickham, W. Jin, M.-C. Asselin, J. Hamelin, M. Varret, D. Allard, et al. NARC-1/PCSK9 and Its Natural Mutants: ZYMOGEN CLEAVAGE AND EFFECTS ON THE LOW DENSITY LIPOPROTEIN (LDL) RECEPTOR AND LDL CHOLESTEROL J. Biol. Chem., November 19, 2004; 279(47): 48865 - 48875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Attie The Mystery of PCSK9 Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1337 - 1339. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |