6533b870fe1ef96bd12cf31b
RESEARCH PRODUCT
Lipid and apoprotein composition of HDL in partial or complete CETP deficiency
Patrizia TarugiMaurizio AvernaPeter M. NilssonGregor DernickElisabeth Von Der MarkAngelo B. CefalùEric J. NiesorLaura Calabresisubject
Settore MED/09 - Medicina InternaApolipoprotein BCholesterol Ester Transfer Proteinmedicine.disease_causereverse phase protein arraychemistry.chemical_compoundExonMutationbiologyHomozygotescavenger receptor class B1size exclusion chromatographyLipidCholesteryl ester transfer proteinLipidstorcetrapibApolipoproteinBiochemistryELISAlipids (amino acids peptides and proteins)hyperalphalipoproteinemiaCardiology and Cardiovascular MedicineLipoproteins HDLHumandalcetrapibmedicine.medical_specialtyHeterozygoteDalcetrapibHypercholesterolemiaapolipoproteinhigh-density lipoproteinInternal medicineCholesterylester transfer proteinmedicineAnimalsHumansCholesteryl ester transfer protein; dalcetrapib; high-density lipoprotein; reverse phase protein array; scavenger receptor class B1; size exclusion chromatography; torcetrapib; apolipoprotein; hyperalphalipoproteinemia; ELISAPharmacologybusiness.industryAnimalPoint mutationCholesterol HDLTorcetrapibnutritional and metabolic diseasesLipid MetabolismCholesterol Ester Transfer Proteinscarbohydrates (lipids)Disease Models AnimalEndocrinologyApolipoproteinschemistrybiology.proteinbusinessLipoproteindescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |