Abstract
Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatography- mass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with <1% false discovery rate from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n = 8) or normal pregnant women (n = 5) was conducted. α2- HS-glycoprotein (AHSG), retinol binding protein 4 (RBP4) and α-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P<0.05). Among these proteins, AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls.
Highlights
Preeclampsia (PE) is a disorder defined by new-onset hypertension and proteinuria after 20 weeks of gestation that can present as late as 4-6 weeks postpartum
Mining of novel biomarkers from human biological fluids poses many challenges that must be overcome through a proteomics approach, such as the wide dynamic range in abundance and complexity of protein components
Recent achievements in proteomics have opened a new chapter in protein biomarker discovery, making a contribution to diagnosis in clinical practice
Summary
Preeclampsia (PE) is a disorder defined by new-onset hypertension and proteinuria after 20 weeks of gestation that can present as late as 4-6 weeks postpartum. PE is generally characterized as follows: 1) during the early period of pregnancy, the placenta releases several growth factors into the maternal circulation, producing excessive systemic inflammation in response to ischemic hypoxia and oxidative stress (Borzychowski et al, 2006). 2), the generalized endothelial dysfunction leads to maternal characteristic symptoms of preeclampsia such as hypertension and proteinuria during the late period of pregnancy (Taylor, 1997). Many groups have been giving special attention to serum proteins related to obesity, low grade inflammation and hypertriacylglycerolemia, which are common symptoms in PE (Smets et al., 2006).
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