Cargando…
Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay
Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564541/ https://www.ncbi.nlm.nih.gov/pubmed/32927635 http://dx.doi.org/10.3390/jcm9092915 |
_version_ | 1783595738090962944 |
---|---|
author | Bedi, Shimpi Garcia, Erwin Jeyarajah, Elias J. Shalaurova, Irina Perez-Matos, Maria Camila Jiang, Z. Gordon Dullaart, Robin P. F. Matyus, Steven P. Kirk, William J. Otvos, James D. Davidson, W. Sean Connelly, Margery A. |
author_facet | Bedi, Shimpi Garcia, Erwin Jeyarajah, Elias J. Shalaurova, Irina Perez-Matos, Maria Camila Jiang, Z. Gordon Dullaart, Robin P. F. Matyus, Steven P. Kirk, William J. Otvos, James D. Davidson, W. Sean Connelly, Margery A. |
author_sort | Bedi, Shimpi |
collection | PubMed |
description | Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. Methods: Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. Results: The assay showed good linearity and precision (2.5–6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. Conclusions: LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease. |
format | Online Article Text |
id | pubmed-7564541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75645412020-10-29 Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay Bedi, Shimpi Garcia, Erwin Jeyarajah, Elias J. Shalaurova, Irina Perez-Matos, Maria Camila Jiang, Z. Gordon Dullaart, Robin P. F. Matyus, Steven P. Kirk, William J. Otvos, James D. Davidson, W. Sean Connelly, Margery A. J Clin Med Article Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. Methods: Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. Results: The assay showed good linearity and precision (2.5–6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. Conclusions: LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease. MDPI 2020-09-10 /pmc/articles/PMC7564541/ /pubmed/32927635 http://dx.doi.org/10.3390/jcm9092915 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bedi, Shimpi Garcia, Erwin Jeyarajah, Elias J. Shalaurova, Irina Perez-Matos, Maria Camila Jiang, Z. Gordon Dullaart, Robin P. F. Matyus, Steven P. Kirk, William J. Otvos, James D. Davidson, W. Sean Connelly, Margery A. Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title | Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title_full | Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title_fullStr | Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title_full_unstemmed | Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title_short | Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay |
title_sort | characterization of lp-z lipoprotein particles and quantification in subjects with liver disease using a newly developed nmr-based assay |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564541/ https://www.ncbi.nlm.nih.gov/pubmed/32927635 http://dx.doi.org/10.3390/jcm9092915 |
work_keys_str_mv | AT bedishimpi characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT garciaerwin characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT jeyarajaheliasj characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT shalaurovairina characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT perezmatosmariacamila characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT jiangzgordon characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT dullaartrobinpf characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT matyusstevenp characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT kirkwilliamj characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT otvosjamesd characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT davidsonwsean characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT connellymargerya characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay |