ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C
| Autor: | Jan Albert Kuivenhoven, Mats Lindahl, Adriaan G. Holleboom, Johannes H.M. Levels, Sofie C. Sundberg, Andrea E. Bochem, Kees Hovingh, Stefan Ljunggren, Maria V. Turkina, Helen Karlsson |
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| Přispěvatelé: | Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Center for Liver, Digestive and Metabolic Diseases (CLDM), Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, Experimental Vascular Medicine, Other departments, Vascular Medicine, Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2014 |
| Předmět: |
Apolipoprotein E
EFFLUX Apolipoprotein B Cell- och molekylärbiologi Clinical Biochemistry PROTEIN Zn-Alpha-2-Glycoprotein ACTIVATION chemistry.chemical_compound High-density lipoprotein polycyclic compounds Prealbumin Electrophoresis Gel Two-Dimensional biology ApoA-I-K131del LECITHIN-CHOLESTEROL ACYLTRANSFERASE Biochemistry and Molecular Biology SR-BI 2DE Cell and molecular biology Phenotype Biochemistry Cardiovascular Diseases CORONARY-ARTERY-DISEASE lipids (amino acids peptides and proteins) Heterozygote medicine.medical_specialty Internal medicine medicine Humans ApoA-I-L202P APOLIPOPROTEIN-A-I Apolipoprotein A-I Cholesterol business.industry Cholesterol HDL Seminal Plasma Proteins nutritional and metabolic diseases Heterozygote advantage MASS-SPECTROMETRY Endocrinology ATHEROSCLEROSIS chemistry alpha 1-Antitrypsin Mutation Lecithin—cholesterol acyltransferase biology.protein business HIGH-DENSITY-LIPOPROTEIN Cell and Molecular Biology Biokemi och molekylärbiologi Lipoprotein |
| Zdroj: | Proteomics. Clinical Applications, 8(3-4), 241-250. WILEY-V C H VERLAG GMBH Proteomics. Clinical applications, 8(3-4), 241-250. Wiley-VCH Verlag |
| ISSN: | 1862-8346 1862-8354 |
| DOI: | 10.1002/prca.201300014 |
| Popis: | PurposeMutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I-L202P and apoA-I-K131del, are present on plasma HDL particles derived from heterozygote carriers and whether this is associated to changes in HDL protein composition.Experimental designPlasma HDL of heterozygotes for either apoA-I-L202P or apoA-I-K131del and family controls was isolated using ultracentrifugation. HDL proteins were separated by 2DE and analyzed by MS.ResultsApoA-I peptides containing apoA-I-L202P or apoA-I-K131del were identified in HDL from heterozygotes. The apoA-I-L202P mutant peptide was less abundant than wild-type peptide while the apoA-I-K131del mutant peptide was more abundant than wild-type peptide in the heterozygotes. Two-dimensional gel electrophoresis analyses indicated that, compared to controls, HDL in apoA-I-L202P carriers contained less apoE and more zinc--2-glycoprotein while HDL from the apoA-I-K131del heterozygotes contained more alpha-1-antitrypsin and transthyretin.Conclusions and clinical relevanceBoth apoA-I-L202P and apoA-I-K131del were identified in HDL. In heterozygotes, these mutations have markedly differential effects on the concentration of wild-type apoA-I in the circulation, as well as the HDL proteome, both of which might affect the clinical phenotype encountered in the heterozygous carriers. |
| Databáze: | OpenAIRE |
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