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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, (...

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Autores principales: 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.
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
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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.
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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
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