DIFFERENTIAL DIAGNOSIS HYPERTENSIVE DISORDERS IN PREGNANCY BASED ON URINE PEPTIDOME PROFILING


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Abstract

Objective. To identify peptide panel allowing to discern different hypertensive disorders in pregnancy. Material and methods. A case-control study was conducted. 64 enrolled women were classified into 4 groups: preeclampsia (PE), chronic hypertension (CAH), PE superimposed on CAH and control. Urine samples derived from each patient were analyzed with liquid chromatography coupled with mass-spectrometry (HPLC-MS/MS). The data obtained were processed using statistical and bioinformatic approaches. Results. For all four groups common typical 36 peptides were identified, which are mainly fragments of collagen (COL1A1;COL3A1, etc.), and one peptide uromodulin (UMOD). For patients with hypertensive disorders (PE, PE superimposed on CAH, CAH) characteristic 34 peptide fragments of collagen (COL1A1;COL3A1, etc.) and alpha-fibrinogen (FGA) were identified. For the group of patients with preeclampsia (PE, PE superimposed on CAH) characteristic panel of 16 peptides were identified: 13-th of which are fragments of the protein alpha-1-antitrypsin (SERPINA1), one peptide is a fragment of alpha-1 chain collagen 1 (COL1A1), 1 - alpha-2-HS-glycoprotein (AHSG), 1 - apolipoprotein A-I (APOA1). Semiquantitative analysis of the data the four groups (PE, PE superimposed on CAH, CAH, the control group) non-parametric tests Kruskal-Wallis and Mann-Whitney test showed the presence of 12 peptides, differentiating at least one pair of groups. Separately, a study was conducted on the peptide profile of urine from a patient with a GAG from the time of diagnosis GAG (32-33 weeks) until delivery (36-37 weeks) in the dynamics. Correlation was established between increased levels of peptides protein SERPINA1(A1AT) and the emergence and increasing severity of PE. Conclusion. In the comparative analysis the panel of 12 peptides which can reliably differentiate hypertensive disorders in pregnant women was formed. Fragments of alpha-1-antitrypsin confirmed their importance as markers of pre-eclampsia suggested by the authors in earlier papers. Demonstrated the dynamics of changes in the peptide profile in the manifestation of clinical signs of PE from the patient to the background of the GAG shows real possibilities of application peptidome urinalysis in clinical practice with the aim of timely diagnosis and predict 'd PE, including PE superimposed on other hypertensive disorders. Further studies are needed to implement the results in clinical practice.

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About the authors

Kamilla T. Muminova

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: kamika91@mail.ru
Junior Researcher, 1st Department of Obstetrical Pathology of Pregnancy Moscow 117997, Ac. Oparina str. 4, Russia

Alexey S. Kononikhin

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia; Moscow Institute of Physics and Technology

Email: konoleha@yandex.ru
Ph.D., scientific employee of the Laboratory of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia

Zulfiya S. Khodzaeva

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: z_khodzhaeva@oparina4.ru
MD, professor, head of the department. 1-st department of obstetrical pathology of pregnancy Moscow 117997, Ac. Oparina str. 4, Russia

Roman G. Shmakov

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: r_shmakov@oparina4.ru
chief physician Moscow 117997, Ac. Oparina str. 4, Russia

Victoria A. Sergeeva

Moscow Institute of Physics and Technology; N.M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences

Email: vik4192@rambler.ru
post-graduate student of the Laboratory of Mass Spectrometry of Biomacromolecules 119336, Russia, Moscow, Kosygina str. 4

Natalia L. Starodubtseva

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.ru
Candidate of Biological Sciences, Head. Laboratory of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia

Anna E. Bugrova

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: anna.bugrova@gmail.com
Ph.D., Senior Researcher, Laboratory of Proteomics of Human Reproduction Moscow 117997, Ac. Oparina str. 4, Russia

Maria I. Indeykina

Moscow Institute of Physics and Technology; N.M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences

Email: mariind@yandex.ru
Junior Researcher, Laboratory of Mass Spectrometry, Biomacromolecules 119336, Russia, Moscow, Kosygina str. 4

Natalia V. Zakharova

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: nvzakharova@yandex.ru
Senior Researcher, Laboratory of Mass Spectrometry Moscow 117997, Ac. Oparina str. 4, Russia

Vladimir E. Frankevich

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
Ph.D., Department of System Biology Moscow 117997, Ac. Oparina str. 4, Russia

Natalia E. Kan

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia; Moscow Institute of Physics and Technology; Skolkovo Institute of Science and Technology Skolkovo Innovation Center

Email: kan-med@mail.ru
MD, head of obstetric department 117997, Russia, Moscow, Ac. Oparina str. 4

Evgeniy N. Nikolaev

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: ennikolaev@rambler.ru
doctor of physical and mathematical sciences, head of Laboratory of mass spectrometry of biomacromolecules Moscow 117997, Ac. Oparina str. 4, Russia

Gennady T. Sukhikh

National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
MD, Academician of the Russian Academy of Sciences, Professor, Director Moscow 117997, Ac. Oparina str. 4, Russia

References

  1. Адамян Л.В., Артымук Н.В., Башмакова Н.В., Белокринницкая Т.E., Беломестное С.Р., Братищев И.В., Вученович Ю.Д., Краснопольский В.К., Куликов A.B., Левит А.Л., Никитина Н.А., Петрухин В.А., Пырегов A.B., Серов В.Н., Сидорова И. С., Филиппов О.С., Ходжаева З.С., Холин А.М., Шешко Е.Л., Шифман Е.М., Шмаков Р.Г. Гипертензивные расстройства во время беременности, в родах и послеродовом периоде. Преэклампсия. Эклампсия. Клинические рекомендации (Протокол лечения). М.; 2016
  2. Рекомендации ВОЗ по профилактике и лечению преэклампсии и эклампсии. Всемирная организация здравоохранения; 2014
  3. Ходжаева З.С., Холин А.М., Вихляева Е.М. Ранняя и поздняя преэклампсия: парадигмы патобиологии и клиническая практика. Акушерство и гинекология. 2013; 10: 4-11.
  4. Ходжаева З.С., Акатьева А.С., Холин А.М., Сафонова А.Д., Вавина О.В., Муминова К.Т. Молекулярные детерминанты развития ранней и поздней преэклампсии. Акушерство и гинекология. 2014; 6: 14-9.
  5. Khodzhaeva Z.S., Kogan E.A., Shmakov R.G., Klimenchenko N.I., Akatyeva A.S., Vavina O.V., Kholin A.M., Muminova K.T., Sukhikh G.T. Clinical and pathogenetic features of early and late onset preeclampsia. J. Matern. Fetal Neonatal Med. 2016; 29(18): 2980-6.
  6. Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. American College of Obstetricians and Gynecologists; 2013.
  7. Holston A.M., Qian C., Yu K.F., Epstein F.H., Karumanchi S.A., Levine R.J. Circulating angiogenic factors in gestational proteinuria without hypertension. Am. J. Obstet. Gynecol. 2009; 200(4): 392. e1-10.
  8. Shirokova V.A., Bugrova A.E., Starodubtseva N.L., Kononikhin A.S., Khodzhaeva Z.S., Muminova K.T., Popov I.A., Frankevich V.E., Nikolaev E.N., Sukhikh G.T. Protein Sci. 2016; 25(1): 123-4. Указ. назв. ст., уточн. где опубл.
  9. Kononikhin A.S., Starodubtseva N.L., Bugrova A.E., Shirokova V.A., Chagovets V.V., Indeykina M.I., Popov I.A., Kostyukevich Y.I., Vavina O.V., Muminova K.T., Khodzhaeva Z.S., Kan N.E., Frankevich V.E., Nikolaev E.N., Sukhikh G.T. An untargeted approach for the analysis of the urine peptidome of women with preeclampsia. J. Proteomics. 2016; 149: 38-43.
  10. Стародубцева Н.Л., Бугрова А.Е., Кононихин А. С., Вавина О.В., Широкова В.А., Наумов В.А., Гаранина И.А., Лагутин В.В., Попов И.А., Логинова Н.С., Ходжаева З.С., Франкевич В.Е., Николаев Е.Н., Сухих Г.Т. Возможность прогнозирования и ранней диагностики преэклампсии по пептидному профилю мочи. Акушерство и гинекология. 2015; 6: 46-52.
  11. Buhimschi I.A., Zhao G., Funai E.F., Harris N., Sasson I.E., Bernstein I.M. et al. Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia. Am. J. Obstet. Gynecol. 2008; 199(5): 551. e1-16.
  12. Wen Q., Liu L.Y., Yang T., Alev C., Wu S., Stevenson D.K. et al. Peptidomic identification of serum peptides diagnosing preeclampsia. PLoS One. 2013; 8(6): e65571.
  13. Carty D.M., Siwy J., Brennand J.E., Zürbig P., Mullen W., Franke J. et al. Urinary proteomics for prediction of preeclampsia. Hypertension. 2011; 57(3): 561-9.
  14. Buhimschi I.A., Nayeri U.A., Zhao G., Shook L.L., Pensalfini A., Funai E.F. et al. Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia. Sci. Transl. Med. 2014; 6(245): 245ra92.
  15. Kouza M., Banerji A., Kolinski A., Buhimschi I.A., Kloczkowski A. Oligomerization of FVFLM peptides and their ability to inhibit beta amyloid peptides aggregation: consideration as a possible model. Phys. Chem. Chem. Phys. 2017; 19(4): 2990-9.
  16. Rossing K., Mischak H., Dakna M., Zürbig P., Novak J., Julian B.A. et al. Urinary proteomics in diabetes and CKD. J. Am. Soc. Nephrol. 2008; 19(7): 1283-90.
  17. Jantos-Siwy J., Schiffer E., Brand K., Schumann G., Rossing K., Delles C. et al. Quantitative urinary proteome analysis for biomarker evaluation in chronic kidney disease. J. Proteome Res. 2008; 8(1): 268-81.
  18. von Zur Muhlen C., Schiffer E., Zuerbig P., Kellmann M., Brasse M., Meert N. et al. Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients. J. Proteome Res. 2008; 8(1): 335-45.
  19. Zimmerli L.U., Schiffer E., Zürbig P., Good D.M., Kellmann M., Mouls L. et al. Urinary proteomic biomarkers in coronary artery disease. Mol. Cell. Proteomics. 2008; 7(2): 290-8.
  20. Delles C., Schiffer E., von Zur Muhlen C., Peter K., Rossing P., Parving H.H. et al. Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals. J. Hypertens. 2010; 28(11): 2316-22.

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