ApoCIII-Enriched LDL in Type 2 Diabetes Displays Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase, and Increased Binding to Biglycan
ApoCIII-Enriched LDL in Type 2 Diabetes Displays Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase, and Increased Binding to Biglycan Anne Hiukka 1 , Marcus Ståhlman 2 , Camilla Pettersson 2 , Malin Levin 2 , Martin Adiels 2 , Susanne Teneberg 3 , Eeva S. Leinonen 1 , Lillemor...
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Published in | Diabetes (New York, N.Y.) Vol. 58; no. 9; pp. 2018 - 2026 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.09.2009
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Subjects | |
Online Access | Get full text |
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Summary: | ApoCIII-Enriched LDL in Type 2 Diabetes Displays Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase,
and Increased Binding to Biglycan
Anne Hiukka 1 ,
Marcus Ståhlman 2 ,
Camilla Pettersson 2 ,
Malin Levin 2 ,
Martin Adiels 2 ,
Susanne Teneberg 3 ,
Eeva S. Leinonen 1 ,
Lillemor Mattsson Hultén 2 ,
Olov Wiklund 2 ,
Matej Orešič 4 ,
Sven-Olof Olofsson 2 ,
Marja-Riitta Taskinen 1 ,
Kim Ekroos 5 and
Jan Borén 2
1 Department of Medicine, Helsinki University Central Hospital and Biomedicum, Helsinki, Finland;
2 Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory and the Department of Molecular and Clinical
Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;
3 Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;
4 Technical Research Centre of Finland VTT, Espoo, Finland;
5 Zora Biosciences, Espoo, Finland.
Corresponding author: Jan Borén, Jan.Boren{at}wlab.gu.se .
A.H. and M.S. contributed equally to this study.
Abstract
OBJECTIVE Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved
are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic
patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was
analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry.
Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [ 3 H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated
with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms.
RESULTS We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was
dependent on a functional site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other
than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII, and
we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased
susceptibility of LDL to hydrolysis and aggregation by sphingomyelinases. In addition, we demonstrated that sialylation of
apoCIII increased with increasing apoCIII content and that sialylation of apoCIII was essential for its proinflammatory properties.
CONCLUSIONS We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes
that could explain the proatherogenic role of apoCIII.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received February 12, 2009.
Accepted May 31, 2009.
© 2009 by the American Diabetes Association. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 A.H. and M.S. contributed equally to this study. |
ISSN: | 0012-1797 1939-327X 1939-327X |
DOI: | 10.2337/db09-0206 |