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Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia
Open AccessArticle

SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity

1
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia
2
Moscow Institute of Physics and Technology, 141701 Moscow, Russia
3
Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia
4
Skolkovo Institute of Science and Technology, Skolkovo, 121205 Moscow, Russia
5
V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia
6
First Moscow State Medical University Named after I.M. Sechenov, 119146 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 914; https://doi.org/10.3390/ijms21030914
Received: 25 December 2019 / Revised: 27 January 2020 / Accepted: 29 January 2020 / Published: 30 January 2020
(This article belongs to the Special Issue Pathogenesis of Pregnancy-Related Complications)
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. View Full-Text
Keywords: preeclampsia; diagnostics; proteomics; mass spectrometry; alpha-1 antitrypsin; syncytiotrophoblast preeclampsia; diagnostics; proteomics; mass spectrometry; alpha-1 antitrypsin; syncytiotrophoblast
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MDPI and ACS Style

Starodubtseva, N.; Nizyaeva, N.; Baev, O.; Bugrova, A.; Gapaeva, M.; Muminova, K.; Kononikhin, A.; Frankevich, V.; Nikolaev, E.; Sukhikh, G. SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity. Int. J. Mol. Sci. 2020, 21, 914. https://doi.org/10.3390/ijms21030914

AMA Style

Starodubtseva N, Nizyaeva N, Baev O, Bugrova A, Gapaeva M, Muminova K, Kononikhin A, Frankevich V, Nikolaev E, Sukhikh G. SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity. International Journal of Molecular Sciences. 2020; 21(3):914. https://doi.org/10.3390/ijms21030914

Chicago/Turabian Style

Starodubtseva, Natalia; Nizyaeva, Natalia; Baev, Oleg; Bugrova, Anna; Gapaeva, Masara; Muminova, Kamilla; Kononikhin, Alexey; Frankevich, Vladimir; Nikolaev, Eugene; Sukhikh, Gennady. 2020. "SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity" Int. J. Mol. Sci. 21, no. 3: 914. https://doi.org/10.3390/ijms21030914

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