| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print February 16, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Medicine, Laval University Medical Center, Quebec City, Quebec G1V 4G2
Corresponding Author: patrick.couture{at}crchul.ulaval.ca
The LDL receptor plays a major role in the regulation of plasma apolipoprotein (apo) B-containing lipoproteins by mediating approximately two thirds of the clearance of these particles. Results from in vitro and human kinetic studies suggest that hepatic oversecretion of apo B100-containing lipoproteins would contribute to the markely elevated plasma concentrations of LDL-cholesterol found in patients with familial hypercholesterolemia (FH). The aim of this study was to examine the kinetics of apo B100 labelled with a stable isotope (L-(5,5,5-D3) leucine) in five normolipidemic male controls and in a unique set of seven well characterized FH subjects which included six FH heterozygous males and one FH homozygous female carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. As compared with controls, the VLDL apo B100 production rate (PR) was increased by 50% in FH heterozygotes and by 109% in the FH homozygote. Furthermore, FH subjects had significantly higher LDL apo B100 pool size (PS) and lower LDL apo B100 fractional catabolic rate (FCR) than controls. We also observed that the FH homozygote had higher IDL apo B100 PS, as well as a higher IDL and LDL apo B100 PR than FH heterozygotes and controls. Taken together, these results suggest that the marked elevation of plasma LDL-cholesterol among FH subjects is attributable to both decreased clearance of LDL and increased hepatic production of apo B100-containing lipoproteins and support the concept that deficiency of LDL receptors could lead to an enhanced conversion of VLDL to LDL which also contributes to the increased LDL apo B 100 PS in FH.
Revised on February 11, 2004
Accepted on February 13, 2004
Increased production rate of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation
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 |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
