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

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 5 12 per group) and difference gel electrophoresis (n 5 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.

Multifactorial analysis of affinity-mass spectrometry data from serum protein samples: A strategy to distinguish patients with preeclampsia from matching control individuals

“…The authors suggested these so-called "cargo proteins" to modify the anti-inflammatory properties of HDL and, thus, might be linked to the relationship between preeclampsia and later coronary artery disease. Interestingly, a recent proteome study of plasma proteins of a "late-onset subgroup" of preeclampsia revealed that transthyretin levels, besides other factors, were elevated compared with those from healthy pregnant controls [49].…”

Low abundance plasma proteins in labour

“…Besides the well-known function of removal of excess cholesterol from the circulation via regulation of hepatic uptake (Belo et al 2004), its function also involves modification of inflammatory responses, including suppressing T cell proliferation, macrophage regulation, lipid antigen presentation facilitation (by CD1) to natural killer T cells, as well as modulation of inflammation and oxidation (Zhang et al 2010). Epidemiological studies have reported that increased levels of APOE are associated with an increased risk of pre-eclampsia, whereas genetic association studies suggested that polymorphisms in APOE are also associated with preeclampsia (Atkinson et al 2009) and spontaneous abortions in patients with endometriosis (Collazo et al 2012). In addition, APOE is involved in inflammatory pathways.…”

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

“…Increased plasma apoE polymorphisms have been reported in women with pre-eclampsia (17,18), however findings relating to apoA1 measurements in pre-eclampsia are conflicting (19,20). To-date, it is not known whether AIBP is expressed in the placenta or altered in pre-eclampsia.…”