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, (...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/9/9/2915 |
| _version_ | 1797554173924868096 |
|---|---|
| author | Shimpi Bedi Erwin Garcia Elias J. Jeyarajah Irina Shalaurova Maria Camila Perez-Matos Z. Gordon Jiang Robin P. F. Dullaart Steven P. Matyus William J. Kirk James D. Otvos W. Sean Davidson Margery A. Connelly |
| author_facet | Shimpi Bedi Erwin Garcia Elias J. Jeyarajah Irina Shalaurova Maria Camila Perez-Matos Z. Gordon Jiang Robin P. F. Dullaart Steven P. Matyus William J. Kirk James D. Otvos W. Sean Davidson Margery A. Connelly |
| author_sort | Shimpi Bedi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T16:26:57Z |
| format | Article |
| id | doaj.art-ebf0ee129af948d5ab22c632c3e3340d |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T16:26:57Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-ebf0ee129af948d5ab22c632c3e3340d2023-11-20T13:11:03ZengMDPI AGJournal of Clinical Medicine2077-03832020-09-0199291510.3390/jcm9092915Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based AssayShimpi Bedi0Erwin Garcia1Elias J. Jeyarajah2Irina Shalaurova3Maria Camila Perez-Matos4Z. Gordon Jiang5Robin P. F. Dullaart6Steven P. Matyus7William J. Kirk8James D. Otvos9W. Sean Davidson10Margery A. Connelly11Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USADivision of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADivision of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Endocrinology, University of Groningen, University Medical Center Groningen, 9713 Groningen, The NetherlandsLaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USACenter for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507, USALaboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USABackground: 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.https://www.mdpi.com/2077-0383/9/9/2915lipoproteinsnuclear magnetic resonance spectroscopycholestasisliver disease |
| spellingShingle | Shimpi Bedi Erwin Garcia Elias J. Jeyarajah Irina Shalaurova Maria Camila Perez-Matos Z. Gordon Jiang Robin P. F. Dullaart Steven P. Matyus William J. Kirk James D. Otvos W. Sean Davidson Margery A. Connelly Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay Journal of Clinical Medicine lipoproteins nuclear magnetic resonance spectroscopy cholestasis liver disease |
| 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 | lipoproteins nuclear magnetic resonance spectroscopy cholestasis liver disease |
| url | https://www.mdpi.com/2077-0383/9/9/2915 |
| work_keys_str_mv | AT shimpibedi characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT erwingarcia characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT eliasjjeyarajah characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT irinashalaurova characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT mariacamilaperezmatos characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT zgordonjiang characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT robinpfdullaart characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT stevenpmatyus characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT williamjkirk characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT jamesdotvos characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT wseandavidson characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay AT margeryaconnelly characterizationoflpzlipoproteinparticlesandquantificationinsubjectswithliverdiseaseusinganewlydevelopednmrbasedassay |