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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http://dx.doi.org/10.3390/jcm9092915 | DOI Listing |
Front Cardiovasc Med
October 2022
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Background: Myriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.
Methods: A pediatric cohort ( = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified.
J Clin Med
February 2022
Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list.
View Article and Find Full Text PDFJ Clin Lipidol
March 2022
Divison of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address:
Background: Alcohol-associated liver disease (ALD) and alcoholic hepatitis (AH) significantly impact the liver, an organ central to the lipid and lipoprotein metabolism.
Objective: To define changes in the lipid and lipoprotein profiles in subjects with alcoholic hepatitis (AH) versus heavy drinkers with normal liver function and to determine the association of the AH-mediated lipoprotein phenotype with AH severity and outcomes.
Methods: AH cases (n=196) and a heavy drinker control group (n=169) were identified in a multicenter, prospective cohort.
Hepatology
April 2022
Division of Gastroenterology, Hepatology, and NutritionDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMassachusettsUSA.
Background And Aims: Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched LDL-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcohol-associated hepatitis (AH) and interrogate the biology behind its formation.
Approach And Results: We measured serum levels of LP-Z using nuclear magnetic resonance spectroscopy, a well-established clinical assay.
J Clin Med
September 2020
Laboratory Corporation of America Holdings (LabCorp), Burlington, NC 27560, USA.
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