Can proteomics improve mother and child outcomes in preeclampsia?

There is no cure for preeclampsia. Treatment is based around risk mitigation, the extent of which is determined by the stage of pregnancy. By and large, treatment is symptomatic rather than interventionist because we do not understand what causes preeclampsia.¹ Proteomics may be able to change that and, in turn, improve the health of both mother and child during pregnancy.

Preeclampsia occurs in 2% to 8% of pregnancies worldwide. Preeclampsia can lead to problems in the liver, kidneys and brain, and with blood clotting. Risks for the baby include poor growth and prematurity; 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia.²

The placenta plays a crucial role in pregnancy. During a healthy pregnancy, maternal spiral arteries are dramatically remodeled. They become widely dilated and lose their responsiveness to vasoconstrictive stimuli. In preeclampsia, spiral artery remodeling is only partial or incomplete.³

In PLoS ONE, Wang et al. (2013) used high-resolution LC-MS/MS to construct a comparative N-glycoproteomic and phosphoproteomic profiling of human placental plasma membrane in normal and preeclamptic pregnancies. Glycoproteins and phosphoproteins are important placental membrane proteins. Both glycosylation and phosphorylation of proteins happens during co-translational or post-translational modification — controlling protein folding, conformational distribution, stability and activity. Additionally, most proteins secreted into plasma are glycosylated or phosphorylated and therefore could be important biomarkers for preeclampsia.⁴

Researchers set out to establish strategies for identifying and quantifying N-glycoproteins and phosphoproteins and for characterizing the glycan and phospho sites of glycoproteins and phosphoproteins in the placental plasma membrane of normal and preeclamptic pregnancies. Labeled deglycosylated peptides were analyzed using the LTQ Orbitrap Velos (Thermo Scientific) mass spectrometer.

After analyzing the mass spectrometry data from the LTQ Orbitrap, researchers found that there was a differential expression of N-glycoprotein peptides and phosphoprotein peptides in normal and preeclamptic placenta plasma membranes. Two N-glycoproteins showed increased expression patterns, while the other three proteins showed decreased expression patterns. Similarly, 15 phosphoproteins had increased expression patterns in preeclamptic placenta plasma membranes, while the expression patterns of the other 23 proteins decreased. A pathway analysis showed that the proteins affected are all involved in pathways important in fetal death, idiopathic hypertension, and hypertension.

This research suggests several possible factors involved in pathological changes in the placenta during preeclampsia. Work still needs to be done verifying these results and mitigating these processes in the clinical setting. Nonetheless, researchers have identified potential biomarkers for preeclampsia and future targets for pathophysiological intervention in preeclampsia.

References

1. Duley, L., Meher, S., Abalos, E. (2006) “Management of Preeclampsia,” British Medical Journal, 332(7539) (pp. 463–8), doi: 10.1136/bmj.332.7539.463.

2. Duley, L. (2009) “The global impact of pre-eclampsia and eclampsia,” Seminars in Perinatology, 33(3) (pp.130–7), doi: 10.1053/j.semperi.2009.02.010.

3. Walker, J.J. (2000) “Pre-eclampsia,” Lancet, (356) (pp. 1260–5), doi: 10.1016/S0140-6736(00)02800-2.

4. Wang, F., et al. (2013) “Comparative N-Glycoproteomic and Phosphoproteomic Profiling of Human Placental Plasma Membrane between Normal and Preeclampsia Pregnancies with High-Resolution Mass Spectrometry,” PLoS ONE, 8(11) (e80480), doi: 10.1371/journal.pone.0080480.

Post Author: Miriam Pollak. Miriam specialised in neuroscience as an undergraduate but traded in lab work for a post graduate degree in science communication.

She has since had a career that has spanned science communication, science education and communications management.

However, Miriam has found her bliss balancing her love of writing and disseminating medical research with managing a multimillion dollar research budget for a childhood cancer charity in Australia.