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LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome.

Journal article
Authors Camilla Pettersson
H Karlsson
Marcus Ståhlman
Thomas Larsson
Björn Fagerberg
Mats Lindahl
Olov Wiklund
Jan Borén
Linda Fogelstrand
Published in Journal of internal medicine
Volume 269
Issue 3
Pages 306-321
ISSN 1365-2796
Publication year 2011
Published at Institute of Medicine, Department of Emergeny and Cardiovascular Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 306-321
Language en
Links dx.doi.org/10.1111/j.1365-2796.2010...
Keywords apoJ; lysozyme; metabolic syndrome; proteomics; small dense LDL; type 2 diabetes
Subject categories Diabetology

Abstract

Objectives  Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyze the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL-particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL. Design  LDL from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro. Results  ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with SEC, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL-particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL. Conclusions  Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase of lysozyme from those with type 2 diabetes.

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