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Papers In Press, published online ahead of print January 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800296-JLR200

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Journal of Lipid Research, Vol. 50, 71-80, January 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Kelly R. Atkinson^1,*, Marion Blumenstein^*, Michael A. Black, Steven H. Wu^*,, Nikola Kasabov, Rennae S. Taylor^**, Garth J. S. Cooper^*,,***, Robyn A. North^** on behalf of the SCOPE Consortium

^* School of Biological Sciences, The University of Auckland, Auckland, New Zealand
Bioinformatics Institute, The University of Auckland, Auckland, New Zealand
Department of Medicine, The University of Auckland, Auckland, New Zealand
^** Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand
Bioinformed Ltd, Dunedin, New Zealand
Knowledge Engineering and Discovery Research Institute, Auckland University of Technology, Auckland, New Zealand
^*** Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, United Kingdom

Published, JLR Papers in Press, August 25, 2008.

This research was funded by the New Zealand Foundation for Research, Science and Technology (UOAX0407) and by the Health Research Council of New Zealand. K.A. was supported by a University of Auckland Doctoral Scholarship.

¹ To whom correspondence should be addressed. e-mail: katkinson{at}hortresearch.co.nz

Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. Because there is no diagnostic test yet available for preeclampsia, we used a proteomic approach to identify novel serum/plasma biomarkers for this condition. We conducted case control studies comparing nulliparous women who developed preeclampsia at 36–38 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Serum/plasma was depleted of six abundant proteins and analyzed by two-dimensional gel electrophoresis (n = 12 per group) and difference gel electrophoresis (n = 12 per group). Differences in abundance of protein spots were detected by univariate and multivariate statistical analyses. Proteins were identified by mass spectrometry and expression of selected proteins was validated by immunoblotting. Proteins whose concentrations were selectively associated with preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c, fibrinogen, transthyretin, and complement factor H-related protein 2. An increase in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms might impair reverse cholesterol transport, contributing to arterial damage. These findings point to a novel mechanistic link between preeclampsia and subsequent cardiovascular disease.

Supplementary key words pregnancy • sialylation • proteomics • serum • plasma

Abbreviations: apoE, apolipoprotein E; 2DE, two-dimensional gel electrophoresis; DIGE, difference gel electrophoresis; ECF, evolving connectionist functions; FDR, false discovery rate; LC, liquid chromatography; MS/MS, tandem mass spectrometry; NSC, nearest shrunken centroids; RFE, recursive feature elimination

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