Protein Profiling of Preeclampsia Placental Tissues

Abstract

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

Comparison of Bcl-xL protein expression in placental trophoblast cells between pregnancy complicated by severe preeclampsia and normotensive pregnancy

“…This was in accordance with a study by Shu et al 11 which found that Bcl-xL expression was downregulated in preterm preeclampsia, but not in term preeclampsia and controls. Allaire et al 10 concluded that the presence of apoptotic marker could be used as a sign of intrauterine hypoxia.…”

A Dormant Microbial Component in the Development of Preeclampsia

“…In a proteomic study of preclamptic vs. normal placentas (696), calretinin was one of the most differentially upregulated proteins ( p  = 1.6 × 10 −13 for preterm PE vs. controls, p  = 8.9 × 10 −7 for term PE vs. controls), and in a manner that correlated with the severity of disease. While calretinin [normally more expressed in neural tissue and mesotheliomas (697)] is not normally seen as a marker of infection, it is, in fact, raised significantly when Chlamydia pneumoniae infects human mesothelial cells (698).…”

Mechanisms of plasminogen activator inhibitor 1 action in stromal remodeling and related diseases

“…Villous syncytiotrophoblast was found responsible for this enhanced PAI-1 expression and reduced perivillous fibrinolysis in patients. In contrast, PAI-2 levels were reduced in placenta 70,76 . Venous umbilical PAI-1 was significantly increased (~10-fold) in hypoxemic placental insufficiency compared to controls.…”

“…Different distribution and time coordination of PAs and their inhibitors (PAI-1 and PAI-2) have important fibrinolytic roles in the early stages of placenta formation as well as its separation from maternal tissue during birth 7,70 . Prostaglandins regulate trophoblast invasion in early pregnancy by stimulation of PAI-1 and inhibition of MMPs expression in stromal cells 71 .…”

“…These pregnancies were accompanied by excessive ThPAI-1 levels in placenta together with abnormal fibrin deposition. Among others, glucocorticoid receptor and RAA signaling pathways are found significantly involved in preterm PE placenta tissues 70,72 . Uterine NK cells produce several cytokines and growth factors that affect trophoblast invasion.…”