Abstract
Preeclampsia (PE) is a severe pregnancy complication, which may be considered as a systemic response in the second half of pregnancy to physiological failures in the first trimester, and can lead to very serious consequences for the health of the mother and fetus. Since PE is often associated with proteinuria, urine proteomic assays may represent a powerful tool for timely diagnostics and appropriate management. High resolution mass spectrometry was applied for peptidome analysis of 127 urine samples of pregnant women with various hypertensive complications: normotensive controls (n = 17), chronic hypertension (n = 16), gestational hypertension (n = 15), mild PE (n = 25), severe PE (n = 25), and 29 patients with complicated diagnoses. Analysis revealed 3869 peptides, which mostly belong to 116 groups with overlapping sequences. A panel of 22 marker peptide groups reliably differentiating PE was created by multivariate statistics, and included 15 collagen groups (from COL1A1, COL3A1, COL2A1, COL4A4, COL5A1, and COL8A1), and single loci from alpha-1-antitrypsin, fibrinogen, membrane-associated progesterone receptor component 1, insulin, EMI domain-containing protein 1, lysine-specific demethylase 6B, and alpha-2-HS-glycoprotein each. ROC analysis of the created model resulted in 88% sensitivity, 96.8% specificity, and receiver operating characteristic curve (AUC) = 0.947. Obtained results confirm the high diagnostic potential of urinary peptidome profiling for pregnancy hypertensive disorders diagnostics.
Highlights
Preeclampsia (PE) is the most severe hypertensive pathology complicating 2–8% of pregnancies and is associated with increased risk of miscarriage, premature birth, disability in the newborns, and development of severe cardiovascular pathologies in women after pregnancy, as well as neonatal and maternal deaths [1,2,3,4]
Using high-performance liquid chromatography with tandem mass spectrometry (HPLC-Mass spectrometry (MS)/MS), we found 35 specific urine peptides originating from SERPINA1, uromodulin, and collagen alpha-1 chains (I and III), which reliably distinguished a Diagnostics 2020, 10, 1039 particular PE group (10—mild PE; 10—severe PE) from normal controls [45]
Based on the analysis of 127 urine samples of pregnant women (including normotesive controls, chronic hypertension (CH), gestational hypertension (GH), moderate PE, and severe PE), and using peptide grouping, we propose a variant of such peptide panel with a high differentiating capacity, which consists of 22 peptide groups and includes markers described earlier
Summary
Preeclampsia (PE) is the most severe hypertensive pathology complicating 2–8% of pregnancies and is associated with increased risk of miscarriage, premature birth, disability in the newborns, and development of severe cardiovascular pathologies in women after pregnancy, as well as neonatal and maternal deaths [1,2,3,4]. Late onset PE (≥34 weeks’ gestation) may occur due to other intrinsic pathologies that may be triggered by pregnancy and are related with abnormal uteroplacental and vascular remodeling, as well as with redistribution of blood flow, which is laid in the first trimester of pregnancy [12,13,14,15]. Predisposing genetic factors relate to polymorphisms in a number of proteins/genes essential for regulation of blood coagulation, vascular endothelial function, blood pressure, inflammation, and immunity, which are essential in other systemic pathologies not associated with pregnancy, such as hypertension, vascular disease, thrombophilia, and systemic inflammation [19,20,21,22,23,24]. The maternal PE syndrome that appears in the second half of pregnancy can be considered as a systemic response to systemic failures in the first trimester, which can occur under various scenarios, depending on different combinations of numerous genetic and non-genetic factors, and may not depend only on a few of them
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