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SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity

Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitryp...

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Autores principales: Starodubtseva, Natalia, Nizyaeva, Natalia, Baev, Oleg, Bugrova, Anna, Gapaeva, Masara, Muminova, Kamilla, Kononikhin, Alexey, Frankevich, Vladimir, Nikolaev, Eugene, Sukhikh, Gennady
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037458/
https://www.ncbi.nlm.nih.gov/pubmed/32019243
http://dx.doi.org/10.3390/ijms21030914
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author Starodubtseva, Natalia
Nizyaeva, Natalia
Baev, Oleg
Bugrova, Anna
Gapaeva, Masara
Muminova, Kamilla
Kononikhin, Alexey
Frankevich, Vladimir
Nikolaev, Eugene
Sukhikh, Gennady
author_facet Starodubtseva, Natalia
Nizyaeva, Natalia
Baev, Oleg
Bugrova, Anna
Gapaeva, Masara
Muminova, Kamilla
Kononikhin, Alexey
Frankevich, Vladimir
Nikolaev, Eugene
Sukhikh, Gennady
author_sort Starodubtseva, Natalia
collection PubMed
description Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitrypsin) in urine remain one of the most promising peptide markers of PE. In this study the diagnostic potential of urinary α1-antitrypsin peptides in PE was evaluated. The urinary peptidome composition of 79 pregnant women with preeclampsia (PE), chronic arterial hypertension (CAH), and a control group was investigated. Mann–Whitney U-test (p < 0.05) revealed seven PE specific SERPINA1 peptides demonstrating 52% sensitivity and 100% specificity. SERPINA1 in urine has been associated with the most severe forms of preeclampsia (p = 0.014), in terms of systolic hypertension (p = 0.01) and proteinuria (p = 0.006). According to Spearman correlation analysis, the normalized intensity of SERPINA1 urinary peptides has a similar diagnostic pattern with known diagnostic PE markers, such as sFLT/PLGF. SERPINA1 peptides were not urinary excreted in superimposed PE (PE with CAH), which is a milder form of PE. An increase in expression of SERPINA1 in the structural elements of the placenta during preeclampsia reflects a protective mechanism against hypoxia. Increased synthesis of SERPINA1 in the trophoblast leads to protein accumulation in fibrinoid deposits. It may block syncytial knots and placenta villi, decreasing trophoblast invasion. Excretion of PE specific SERPINA1 peptides is associated with syncytiotrophoblast membrane destruction degradation and increased SERPINA1 staining. It confirms that the placenta could be the origin of SERPINA1 peptides in urine. Significant correlation (p < 0.05) of SERPINA1 expression in syncytiotrophoblast membrane and cytoplasm with the main clinical parameters of severe PE proves the role of SERPINA1 in PE pathogenesis. Estimation of SERPINA1 peptides in urine can be used as a diagnostic test of the severity of the condition to determine further treatment, particularly the need for urgent surgical delivery.
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spelling pubmed-70374582020-03-11 SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity Starodubtseva, Natalia Nizyaeva, Natalia Baev, Oleg Bugrova, Anna Gapaeva, Masara Muminova, Kamilla Kononikhin, Alexey Frankevich, Vladimir Nikolaev, Eugene Sukhikh, Gennady Int J Mol Sci Article Preeclampsia (PE) is a multisystem disorder associated with pregnancy and its frequency varies from 5 to 20 percent of pregnancies. Although a number of preeclampsia studies have been carried out, there is no consensus about disease etiology and pathogenesis so far. Peptides of SERPINA1 (α1-antitrypsin) in urine remain one of the most promising peptide markers of PE. In this study the diagnostic potential of urinary α1-antitrypsin peptides in PE was evaluated. The urinary peptidome composition of 79 pregnant women with preeclampsia (PE), chronic arterial hypertension (CAH), and a control group was investigated. Mann–Whitney U-test (p < 0.05) revealed seven PE specific SERPINA1 peptides demonstrating 52% sensitivity and 100% specificity. SERPINA1 in urine has been associated with the most severe forms of preeclampsia (p = 0.014), in terms of systolic hypertension (p = 0.01) and proteinuria (p = 0.006). According to Spearman correlation analysis, the normalized intensity of SERPINA1 urinary peptides has a similar diagnostic pattern with known diagnostic PE markers, such as sFLT/PLGF. SERPINA1 peptides were not urinary excreted in superimposed PE (PE with CAH), which is a milder form of PE. An increase in expression of SERPINA1 in the structural elements of the placenta during preeclampsia reflects a protective mechanism against hypoxia. Increased synthesis of SERPINA1 in the trophoblast leads to protein accumulation in fibrinoid deposits. It may block syncytial knots and placenta villi, decreasing trophoblast invasion. Excretion of PE specific SERPINA1 peptides is associated with syncytiotrophoblast membrane destruction degradation and increased SERPINA1 staining. It confirms that the placenta could be the origin of SERPINA1 peptides in urine. Significant correlation (p < 0.05) of SERPINA1 expression in syncytiotrophoblast membrane and cytoplasm with the main clinical parameters of severe PE proves the role of SERPINA1 in PE pathogenesis. Estimation of SERPINA1 peptides in urine can be used as a diagnostic test of the severity of the condition to determine further treatment, particularly the need for urgent surgical delivery. MDPI 2020-01-30 /pmc/articles/PMC7037458/ /pubmed/32019243 http://dx.doi.org/10.3390/ijms21030914 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Starodubtseva, Natalia
Nizyaeva, Natalia
Baev, Oleg
Bugrova, Anna
Gapaeva, Masara
Muminova, Kamilla
Kononikhin, Alexey
Frankevich, Vladimir
Nikolaev, Eugene
Sukhikh, Gennady
SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title_full SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title_fullStr SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title_full_unstemmed SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title_short SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity
title_sort serpina1 peptides in urine as a potential marker of preeclampsia severity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037458/
https://www.ncbi.nlm.nih.gov/pubmed/32019243
http://dx.doi.org/10.3390/ijms21030914
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