Abstract
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.
Highlights
Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction
Two separate case control studies were conducted using either serum (2DE) or plasma (DIGE) collected from women diagnosed with preeclampsia compared with healthy pregnant women matched by gestational age at sampling
Spot members of these classification models were identified by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) as apoC-II, retinol binding protein, apolipoprotein E (apoE) basic isoform, apoE acidic isoform, complement factor C3c, and inter-a-trypsin inhibitor H4 (Fig. 1 and Table 3)
Summary
Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. 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. Serum clusterin was reportedly increased in preeclampsia with fetal growth restriction [6] These studies indicated the potential of proteomic approaches, only small numbers of women with severe disease were included. Combinations of univariate statistical methods and multivariate classification methodologies have recently been proposed for the analysis of complex proteomic datasets [8] This approach pinpoints protein combinations that may be able to distinguish between healthy and disease states [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
