on January 29, 2004
Published online before print January 29, 2004, doi: 10.1161/01.ATV.0000119681.47218.a4
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 5, 2003
Accepted on January 20, 2004
Subclasses of Low-Density Lipoprotein and Very Low-Density Lipoprotein in Familial Combined Hyperlipidemia: Relationship to Multiple Lipoprotein Phenotype
A. M. Georgieva ;
From the Cardiovascular Research Institute Maastricht, Laboratory of Molecular Metabolism and Endocrinology, Department of Medicine, University of Maastricht, The Netherlands; and Donner Laboratory (R.M.K.), Lawrence Berkeley National Laboratory, University of California, Berkeley.
* To whom correspondence should be addressed. E-mail: tdb{at}sint.azm.nl.
Objective--The present study addresses the presence of distinct metabolic phenotypes in familial combined hyperlipidemia (FCHL) in relation to small dense low-density lipoprotein (sd LDL) and very low-density lipoprotein (VLDL) subclasses.
Methods and Results--Hyperlipidemic FCHL relatives (n=72) were analyzed for LDL size by gradient gel electrophoresis. Pattern B LDL (sd LDL, particle size <258 Å) and pattern A LDL (buoyant LDL, particle size 
258 Å) were defined. Analyses showed bimodal distribution of LDL size associated with distinct phenotypes. Subjects with predominantly large, buoyant LDL showed a hypercholesterolemic phenotype and the highest apo B levels. Subjects with predominantly sd LDL showed a hypertriglyceridemic, low high-density lipoprotein (HDL) cholesterol phenotype, with moderately elevated apoB, total cholesterol level, and LDL cholesterol level. Subjects with both buoyant LDL and sd LDL (pattern AB, n=7) showed an intermediate phenotype, with high normal plasma triglycerides. VLDL subfraction analysis showed that the sd LDL phenotype was associated with a 10-times higher number of VLDL1 particles of relatively lower apo AI and apo E content, as well as smaller VLDL2 particles, in combination with increased plasma insulin concentration in comparison to pattern A.
Conclusions--The present observations underscore the importance of the VLDL triglyceride metabolic pathway in FCHL as an important determinant of the phenotypic heterogeneity of the disorder.
Key words: sd LDL • apolipoprotein B • triglycerides • insulin resistance • VLDL
This article has been cited by other articles:
 |
|
 |
|
  M. Adiels, S.-O. Olofsson, M.-R. Taskinen, and J. Boren Overproduction of Very Low-Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1225 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Morello, T. W.A. de Bruin, J. I. Rotter, R. E. Pratt, C. J.H. van der Kallen, G. A. Hladik, V. J. Dzau, C.-C. Liew, and Y.-D. I. Chen Differential Gene Expression of Blood-Derived Cell Lines in Familial Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2149 - 2154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Cantor, T. de Bruin, N. Kono, S. Napier, A. van Nas, H. Allayee, and A. J. Lusis Quantitative Trait Loci for Apolipoprotein B, Cholesterol, and Triglycerides in Familial Combined Hyperlipidemia Pedigrees Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1935 - 1941. [Abstract] [Full Text] [PDF]
|
|