Identification of differentially expressed proteins associated with the development of preeclampsia by proteomics using multiple reaction monitoring (MRM)-based quantification

Abstract

Introduction: Defective deep placentation is an abnormal transformation of the spiral arteries in the junctional zone of the myometrium. It results in significant obstetrical complications such as preeclampsia, fetal growth restriction, placental infarcts with fetal death, placental abruption, preterm labor, and premature rupture of membranes. Preeclampsia is a representative disease of those with defective deep placentation. We performed proteomic analysis including multiple reaction monitoring (MRM)-based quantification with maternal plasma samples at the estimated time of deep placentation. The aim of this study was to determine the proteomic biomarkers associated with the development of preeclampsia.

Methods: A case-control study was conducted. Maternal plasma was obtained from women with singleton pregnancies between 16 and 21 weeks of gestation in which deep placentation appeared to have occurred during that period. Thirteen women subsequently diagnosed with preeclampsia were selected as cases and an equal number of matched women who delivered at term without complications served as controls. Differential proteome profiling was conducted with the previously stored plasma using an LTQ-Velos mass spectrometer. Proteins potentially associated with preeclampsia were further validated by multiple reaction monitoring (MRM)-targeted proteome analysis.

Results: We identified a large group of proteins differentially expressed in the cases compared to the controls by proteome profiling. Subsequently, MRM-targeted proteome analysis resulted in two significantly up-regulated proteins (complement C1s subcomponent and alpha-1 microglobulin / bikunin precursor (AMBP)).

Conclusions: We identified proteins that are differentially expressed during deep placentation in the maternal plasma of those who subsequently developed preeclampsia. We propose that these proteins may be involved in the remodeling process of the spiral arteries even before the manifestation of clinical disease. These proteins could be served as potential biomarkers to predict obstetrical complications associated with defective deep placentation.