Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia.
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. We examined the relationship between LDL heterogeneity and plasma CETP mass in familial hypercholesterolemia (FH). LDL particles were characterized by polyacrylamide gradient gel electrophoresis in a total of 259 FH heterozygotes and 208 nonFH controls. CETP mass was measured by enzyme-linked immunosorbent assay 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 A; 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.
Hogue
Jean-Charles
JC
Lipid Research Center, CHUL Research Center and Laval University, Québec, Canada.
Lamarche
Benoît
B
Gaudet
Daniel
D
Larivière
Mathieu
M
Tremblay
André J
AJ
Bergeron
Jean
J
Lemieux
Isabelle
I
Després
Jean-Pierre
JP
Gagné
Claude
C
Couture
Patrick
P
D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis; D001797:Blood Protein Electrophoresis; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D004198:Disease Susceptibility; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D008297:Male; D008970:Molecular Weight; D010316:Particle Size
D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008077:Lipoproteins, LDL