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Lipid and Apoprotein Composition of HDL in Partial or Complete CETP Deficiency

Niesor, Eric J.; von der Mark, Elisabeth; Calabresi, Laura; Averna, Maurizio; Cefalu, Angelo B.; Tarugi, Patrizia; Nilsson, Peter LU and Dernick, Gregor (2012) In Current Vascular Pharmacology 10(4). p.422-431
Abstract
Hyperalphalipoproteinemia, as observed in patients who are either homozygous or heterozygous for cholesteryl ester transfer protein (CETP) deficiency, has been shown to be associated with striking changes in apolipoprotein size distribution, namely, of high-density lipoprotein (HDL) and HDL-like particles. We compared the effect of varying degrees of CETP activity on the HDL apolipoprotein profile in Caucasian CETP-deficient subjects and following pharmacological decrease in CETP activity, using Size Exclusion Chromatography followed by Reverse Phase Protein Array (SEC RPA). The main HDL-associated apolipoproteins (Apo), i.e. ApoA-I, ApoA-II, ApoC-I, and ApoC-III, co-eluted with the HDL peak. The presence of a HDL-like peak migrating... (More)
Hyperalphalipoproteinemia, as observed in patients who are either homozygous or heterozygous for cholesteryl ester transfer protein (CETP) deficiency, has been shown to be associated with striking changes in apolipoprotein size distribution, namely, of high-density lipoprotein (HDL) and HDL-like particles. We compared the effect of varying degrees of CETP activity on the HDL apolipoprotein profile in Caucasian CETP-deficient subjects and following pharmacological decrease in CETP activity, using Size Exclusion Chromatography followed by Reverse Phase Protein Array (SEC RPA). The main HDL-associated apolipoproteins (Apo), i.e. ApoA-I, ApoA-II, ApoC-I, and ApoC-III, co-eluted with the HDL peak. The presence of a HDL-like peak migrating between the ApoB-LDL and ApoA-I-HDL was identified in a Caucasian patient with homozygosity for a point mutation in exon 2 of the CETP gene (c. 109 C > T) resulting in a premature termination codon (R37X) and complete CETP deficiency. This HDL-like peak was not observed either in healthy volunteers treated with the CETP modulator dalcetrapib, patients heterozygous for the same mutation, or in patients heterozygous with G165X mutations. SEC RPA offers the possibility to investigate the distribution of a large number of apolipoproteins simultaneously under non-denaturing separation in normal and dyslipidemic subjects. This is only limited by the availability of antibodies against specific apolipoproteins to be investigated. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
size exclusion chromatography, torcetrapib, Cholesteryl ester transfer protein, high-density, dalcetrapib, scavenger receptor class B1, reverse phase protein array, lipoprotein
in
Current Vascular Pharmacology
volume
10
issue
4
pages
422 - 431
publisher
Bentham Science Publishers
external identifiers
  • wos:000305650400004
  • scopus:84861673540
ISSN
1570-1611
language
English
LU publication?
yes
id
f2b335eb-6377-46a5-b944-d7f1d361700e (old id 2863723)
date added to LUP
2012-08-01 09:42:54
date last changed
2017-01-01 03:00:54
@article{f2b335eb-6377-46a5-b944-d7f1d361700e,
  abstract     = {Hyperalphalipoproteinemia, as observed in patients who are either homozygous or heterozygous for cholesteryl ester transfer protein (CETP) deficiency, has been shown to be associated with striking changes in apolipoprotein size distribution, namely, of high-density lipoprotein (HDL) and HDL-like particles. We compared the effect of varying degrees of CETP activity on the HDL apolipoprotein profile in Caucasian CETP-deficient subjects and following pharmacological decrease in CETP activity, using Size Exclusion Chromatography followed by Reverse Phase Protein Array (SEC RPA). The main HDL-associated apolipoproteins (Apo), i.e. ApoA-I, ApoA-II, ApoC-I, and ApoC-III, co-eluted with the HDL peak. The presence of a HDL-like peak migrating between the ApoB-LDL and ApoA-I-HDL was identified in a Caucasian patient with homozygosity for a point mutation in exon 2 of the CETP gene (c. 109 C > T) resulting in a premature termination codon (R37X) and complete CETP deficiency. This HDL-like peak was not observed either in healthy volunteers treated with the CETP modulator dalcetrapib, patients heterozygous for the same mutation, or in patients heterozygous with G165X mutations. SEC RPA offers the possibility to investigate the distribution of a large number of apolipoproteins simultaneously under non-denaturing separation in normal and dyslipidemic subjects. This is only limited by the availability of antibodies against specific apolipoproteins to be investigated.},
  author       = {Niesor, Eric J. and von der Mark, Elisabeth and Calabresi, Laura and Averna, Maurizio and Cefalu, Angelo B. and Tarugi, Patrizia and Nilsson, Peter and Dernick, Gregor},
  issn         = {1570-1611},
  keyword      = {size exclusion chromatography,torcetrapib,Cholesteryl ester transfer protein,high-density,dalcetrapib,scavenger receptor class B1,reverse phase protein array,lipoprotein},
  language     = {eng},
  number       = {4},
  pages        = {422--431},
  publisher    = {Bentham Science Publishers},
  series       = {Current Vascular Pharmacology},
  title        = {Lipid and Apoprotein Composition of HDL in Partial or Complete CETP Deficiency},
  volume       = {10},
  year         = {2012},
}