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J Clin Med. 2020 Sep 10;9(9). doi: 10.3390/jcm9092915.

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay.

Journal of clinical medicine

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

Affiliations

  1. Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507, USA.
  2. Laboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USA.
  3. Division of Gastroenterology & Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  4. Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9713 Groningen, The Netherlands.

PMID: 32927635 PMCID: PMC7564541 DOI: 10.3390/jcm9092915

Abstract

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.

Keywords: cholestasis; lipoproteins; liver disease; nuclear magnetic resonance spectroscopy

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