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SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity.
Int J Mol Sci. 2020 Jan 30; 21(3)IJ

Abstract

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.

Authors+Show Affiliations

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia. Moscow Institute of Physics and Technology, Moscow 141701, Russia. V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia. V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Russia. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia. V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Russia. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Russia. Skolkovo Institute of Science and Technology, Skolkovo, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia.V.L. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, Russia. Skolkovo Institute of Science and Technology, Skolkovo, Russia.National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow 117997, Russia. First Moscow State Medical University named after I.M. Sechenov, Moscow, Russia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32019243

Citation

Starodubtseva, Natalia, et al. "SERPINA1 Peptides in Urine as a Potential Marker of Preeclampsia Severity." International Journal of Molecular Sciences, vol. 21, no. 3, 2020.
Starodubtseva N, Nizyaeva N, Baev O, et al. SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity. Int J Mol Sci. 2020;21(3).
Starodubtseva, N., Nizyaeva, N., Baev, O., Bugrova, A., Gapaeva, M., Muminova, K., Kononikhin, A., Frankevich, V., Nikolaev, E., & Sukhikh, G. (2020). SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity. International Journal of Molecular Sciences, 21(3). https://doi.org/10.3390/ijms21030914
Starodubtseva N, et al. SERPINA1 Peptides in Urine as a Potential Marker of Preeclampsia Severity. Int J Mol Sci. 2020 Jan 30;21(3) PubMed PMID: 32019243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SERPINA1 Peptides in Urine as A Potential Marker of Preeclampsia Severity. AU - Starodubtseva,Natalia, AU - Nizyaeva,Natalia, AU - Baev,Oleg, AU - Bugrova,Anna, AU - Gapaeva,Masara, AU - Muminova,Kamilla, AU - Kononikhin,Alexey, AU - Frankevich,Vladimir, AU - Nikolaev,Eugene, AU - Sukhikh,Gennady, Y1 - 2020/01/30/ PY - 2019/12/25/received PY - 2020/01/27/revised PY - 2020/01/29/accepted PY - 2020/2/6/entrez PY - 2020/2/6/pubmed PY - 2020/2/6/medline KW - alpha-1 antitrypsin KW - diagnostics KW - mass spectrometry KW - preeclampsia KW - proteomics KW - syncytiotrophoblast JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 3 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32019243/SERPINA1_Peptides_in_Urine_as_A_Potential_Marker_of_Preeclampsia_Severity L2 - https://www.mdpi.com/resolver?pii=ijms21030914 DB - PRIME DP - Unbound Medicine ER -
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