J. Lipid Res.
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A more recent version of this article appeared on June 1, 2004

Papers In Press, published online ahead of print March 16, 2004
J. Lipid Res., doi:10.1194/jlr.M300420-JLR200
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Submitted on October 6, 2003
Revised on February 11, 2004
Accepted on March 10, 2004

Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia

Jean-Charles Hogue, Benoît Lamarche, Daniel Gaudet, Mathieu Larivière, André J. Tremblay, Jean Bergeron, Isabelle Lemieux, Jean-Pierre Després, Claude Gagné, and Patrick Couture

Department of Medicine, Laval University Medical Center, Quebec City, Quebec G1V 4G2

Corresponding Author: patrick.couture{at}crchul.ulaval.ca

Small, dense LDL particles have been associated with an increased risk of coronary artery disease and cholesteryl ester transfer protein (CETP) has been suggested to play a role in LDL particle remodeling. The purpose of the present study was to examine the relationship between the electrophoretic characteristics of LDL particles and plasma CETP mass concentrations in familial hypercholesterolemia (FH). LDL particles were characterized by polyacrylamide gradient gel electrophoresis (PAGGE) in a total of 259 FH heterozygotes and 208 non-FH controls. CETP mass was measured by ELISA in a subgroup of 240 participants which included 120 FH patients matched with 120 controls. As compared with controls, FH subjects had an 11% higher CETP mass. Moreover, LDL-Peak Particle Diameter (LDL-PPD) was significantly smaller in FH heterozygotes than in controls (258.1±4.8 vs 259.2±4.1 Å; P=0.01) after adjustment for covariates. There was also an inverse relationship between LDL-PPD and CETP mass (R=-0.15; P=0.02) and this relationship was abolished by adjustment for the FH/Control status, indicating that LDL-PPD changes in FH are mediated, at least in part, by an increase in plasma CETP mass concentrations. These results suggest that increased plasma CETP mass concentrations could lead to significant LDL particle remodeling in FH heterozygotes and could contribute to the pathogenesis of atherosclerosis in these patients by decreasing LDL-PPD which represents the diameter of the most abundant subclass of LDL particles.


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