Plasma proteome cluster analysis in pregnant women with preeclampsia

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective: To investigate the molecular biology and development of preeclampsia through proteomic profiling of the blood plasma of pregnant women using cluster analysis of proteins.

Materials and methods: The study comprised 27 pregnant women, including 15 patients with healthy pregnancies (control group, median gestational age 39.5 (39.5; 40.0) weeks) and 12 patients with severe preeclampsia (study group, median gestational age 32.1 (29;35) weeks). The baseline evaluations included clinical, laboratory, and instrumental methods. The proteomic profile of blood plasma was determined using ultra-high-resolution liquid chromatography mass spectrometry. Protein cluster analysis was performed using the DAVID online tool.

Results: Plasma proteomic analysis identified approximately 1500 proteins in each sample. Differential differences were found for 317 proteins in pregnant women with preeclampsia, and changes in 113 of them were statistically significant (70 proteins with overexpression and 43 proteins with reduced expression). Cluster analysis of plasma proteins differentiated in preeclampsia allowed the identification of nine of the largest clusters, indicating a significant role of abnormalities in the complement and coagulation systems, inflammatory and immune responses, metabolic disorders, and changes in cellular processes (particularly endoplasmic reticulum function) in the pathogenesis of preeclampsia. Data are available via ProteomeXchange with the identifier PXD036175.

Conclusion: The proteomic profile of maternal blood in preeclampsia differs significantly from that in uncomplicated pregnancies and is characterized by the variability of changes reflecting multiple and multidirectional disturbances of biological processes and molecular functions.

Full Text

Restricted Access

About the authors

Natalya A. Nikitina

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: natnikitina@list.ru
ORCID iD: 0000-0001-8659-9963

Dr. Med. Sci., Professor, Department of Obstetrics and Gynaecology No. 1

Russian Federation, Moscow

Iraida S. Sidorova

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: sidorovais@yandex.ru
ORCID iD: 0000-0003-2209-8662

Dr. Med. Sci., Professor, Academician of RAS, Merited Scholar of the Russian Federation, Department of Obstetrics and Gynaecology No. 1

Russian Federation, Moscow

Rustam Kh. Ziganshin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the RAS

Email: rustam.ziganshin@gmail.com
ORCID iD: 0000-0002-7931-519X

PhD, Senior Researcher, Head of the Group of Mass Spectrometry

Russian Federation, Moscow

Marina A. Kir'yanova

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: kiryanova.marina8@mail.ru
ORCID iD: 0000-0001-6950-5283

PhD Student at the Department of Obstetrics and Gynecology No. 1

Russian Federation, Moscow

Mikhail B. Ageev

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: mikhaageev@yandex.ru
ORCID iD: 0000-0002-6603-804X

PhD, Teaching Assistant at the Department of Obstetrics and Gynecology No. 1

Russian Federation, Moscow

References

  1. Сидорова И.С., Никитина Н.А. Обоснование современной концепции развития преэклампсии. Акушерство и гинекология. 2019; 4: 26-33. [Sidorova I.S., Nikitina N.A. Validation of the modern concept of the development of preeclampsia. Obstetrics and Gynecology. 2019; (4): 26-33. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.4.26-33.
  2. Benny P.A., Alakwaa F.M., Schlueter R.J., Lassiter C.B., Garmire L.X. A review of omics approaches to study preeclampsia. Placenta. 2020; 92: 17-27. https://dx.doi.org/ 10.1016/j.placenta.2020.01.008.
  3. Navajas R., Corrales F., Paradela A. Quantitative proteomics-based analyses performed on pre-eclampsia samples in the 2004-2020 period: a systematic review. Clin. Proteomics. 2021; 18(1): 6. https://dx.doi.org/10.1186/ s12014-021-09313-1.
  4. Sun Y.V., Hu Y.J. Integrative analysis of multi-omics data for discovery and functional studies of complex human diseases. Adv. Genet. 2016; 93: 147-90. https://dx.doi.org/10.1016/bs.adgen.2015.11.004.
  5. Никитина Н.А., Сидорова И.С., Агеев М.Б., Тимофеев С.А., Кирьянова М.А., Морозова Е.А. Новые технологии в решении проблем преэклампсии. Акушерство и гинекология. 2022; 10: 5-13. [Nikitina N.A., Sidorova I.S., Ageev M.B., Timofeev S.A., Kiryanova M.A., Morozova E.A. New technologies in solving the problems of preeclampsia. Obstetrics and Gynecology. 2022; (10): 5-13. (in Russian)]. https://dx.doi.org/10.18565/aig.2022.10.5-13.
  6. Deutsch E.W., Omenn G.S., Sun Z., Maes M., Pernemalm M., Palaniappan K.K. et al. Advances and utility of the human plasma proteome. J. Proteome Res. 2021; 20(12): 5241-63. https://dx.doi.org/10.1021/acs.jproteome.1c00657.
  7. Romero R., Erez O., Maymon E., Chaemsaithong P., Xu Z., Pacora P. et al. The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study. Am. J. Obstet. Gynecol. 2017; 217(1): 67.e1-67.e21. https://dx.doi.org/10.1016/j.ajog.2017.02.037.
  8. Aghaeepour N., Lehallier B., Baca Q., Ganio E.A., Wong R.J., Ghaemi M.S. et al. A proteomic clock of human pregnancy. Am. J. Obstet. Gynecol. 2018; 218(3): 347.e1-347.e14. https://dx.doi.org/10.1016/j.ajog.2017.12.208.
  9. Tarca A.L., Romero R., Benshalom-Tirosh N., Than N.G., Gudicha D.W., Done B. et al. The prediction of early preeclampsia: Results from a longitudinal proteomics study. PLoS One. 2019; 14(6): e0217273. https://dx.doi.org/10.1371/journal.pone.0217273.
  10. Hedman A.M., Lundholm C., Andolf E., Pershagen G., Fall T., Almqvist C. Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study. Sci. Rep. 2020; 10(1): 17819. https://dx.doi.org/10.1038/s41598-020-74722-5.
  11. 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. [Starodubtseva N.L., Bugrova A.E., Kononikhin A.S., Vavina O.V., Shirokova V.A., Naumov V.A., Garanina I.A., Lagutin V.V., Popov I.A., Loginova N.S., Khodzhaeva Z.S., Frankevich V.E., Nikolaev E.N., Sukhikh G.T. Possibility for the prediction and early diagnosis of preeclampsia from the urinary peptide profile. Obstetrics and Gynecology. 2015; (6): 46-52. (in Russian)].
  12. Прокопенко В.М. Применение протеомного анализа в акушерстве (первые результаты исследований). Российский вестник акушера-гинеколога. 2016; 16(1): 28-32. [Prokopenko V.M. Use of proteomic analysis in obstetrics: first results of investigations. Russian Bulletin of Obstetrician-Gynecologist. 2016; 16(1): 28-32. (in Russian)]. https://dx.doi.org/10.17116/rosakush201616128-32.
  13. Michalczyk M., Celewicz A., Celewicz M., Woźniakowska-Gondek P., Rzepka R. The Role of Inflammation in the Pathogenesis of Preeclampsia. Mediators Inflamm. 2020; 2020: 3864941. https://dx.doi.org/10.1155/2020/3864941.
  14. Cavaillon J.M., Sansonetti P., Goldman M. 100th Anniversary of Jules Bordet's Nobel Prize: tribute to a founding father of immunology. Front. Immunol. 2019; 10: 2114. https://dx.doi.org/10.3389/fimmu.2019.02114.
  15. Youssef L., Miranda J., Blasco M., Paules C., Crovetto F., Palomo M. et al. Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics. Sci. Rep. 2021; 11(1): 3048. https://dx.doi.org/10.1038/s41598-021-82733-z.
  16. Regal J.F., Gilbert J.S., Burwick R.M. The complement system and adverse pregnancy outcomes. Mol. Immunol. 2015; 67(1): 56-70. https://dx.doi.org/10.1016/j.molimm.2015.02.030.
  17. Сидорова И.С., Никитина Н.А., Унанян А.Л., Агеев М.Б., Кокин А.А. Система комплемента при физиологической беременности. Акушерство и гинекология. 2021; 6: 14-20. [Sidorova I.S., Nikitina N.A., Unanyan A.L., Ageev M.B., Kokin A.A. The complement system during physiological pregnancy. Obstetrics and Gynecology. 2021; (6): 14-20. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.6.14-20.
  18. Сидорова И.С., Никитина Н.А., Унанян А.Л., Агеев М.Б., Кокин А.А. Система комплемента при беременности, осложненной преэклампсией. Акушерство и гинекология. 2021; 8: 5-12. [Sidorova I.S., Nikitina N.A., Unanyan A.L., Ageev M.B., Kokin A.A. The complement system in preeclampsia-complicated pregnancy. Obstetrics and Gynecology. 2021; (8): 5-12. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.8.5-12.
  19. Сидорова И.С., Никитина Н.А., Агеев М.Б., Кокин А.А., Кирьянова М.А. Дисрегуляция системы комплемента при развитии преэклампсии. Акушерство и гинекология. 2022; 2: 46-58. [Sidorova I.S., Nikitina N.A., Ageev M.B., Kokin A.A., Kir'yanova M.A. Complement system dysregulation in patients with preeclampsia. Obstetrics and Gynecology. 2022; (2): 46-58. (in Russian)]. https://dx.doi.org/10.18565/aig.2022.2.46-58.
  20. He Y.D., Xu B.N., Wang M.L., Wang Y.Q., Yu F., Chen Q. et al. Dysregulation of complement system during pregnancy in patients with preeclampsia: A prospective study. Mol. Immunol. 2020; 122: 69-79. https://dx.doi.org/10.1016/j.molimm.2020.03.021.
  21. Yonekura Collier A.R., Zsengeller Z., Pernicone E., Salahuddin S., Khankin E.V., Karumanchi S.A. Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia. Hypertens Pregnancy. 2019; 38(3): 193-9. https://dx.doi.org/10.1080/10641955.2019.1640725.
  22. Jia C., Tan Y., Zhao M. The complement system and autoimmune diseases. Chronic Dis. Transl. Med. 2022; 8(3): 184-90. https://dx.doi.org/10.1002/cdt3.24.
  23. Oncul S., Afshar-Kharghan V. The interaction between the complement system and hemostatic factors. Curr. Opin. Hematol. 2020; 27(5): 341-52. https://dx.doi.org/10.1097/MOH.0000000000000605.
  24. Krisinger M.J., Goebeler V., Lu Z., Meixner S.C., Myles T., Pryzdial E.L. et al. Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway. Blood. 2012; 120(8): 1717-25. https://dx.doi.org/10.1182/blood-2012-02-412080.
  25. Ritis K., Doumas M., Mastellos D., Micheli A., Giaglis S., Magotti P. et al. A novel C5a receptor-tissue factor cross-talk in neutrophils links innate immunity to coagulation pathways. J. Immunol. 2006; 177(7): 4794-802. https://dx.doi.org/10.4049/jimmunol.177.7.4794.
  26. Huntington J.A. Chemistry and biology of heparin and heparan sulfate. Elsevier; 2005: 367-98. https://dx.doi.org/10.1016/B978-008044859-6/50014-9.
  27. Bano S., Fatima S., Ahamad S., Ansari S., Gupta D., Tabish M. Identification and characterization of a novel isoform of heparin cofactor II in human liver. IUBMB Life. 2020; 72(10): 2180-93. https://dx.doi.org/10.1002/ iub.2361.
  28. Čápová I., Salaj P., Hrachovinová I. Hereditary antithrombin deficiency in pregnancy - severe thrombophilic disorder as a danger for mother and foetus. Ceska Gynekol. 2021; 86(3): 175-82. https://dx.doi.org/10.48095/ cccg2021175.
  29. Thomas M.R., Storey R.F. The role of platelets in inflammation. Thromb. Haemost. 2015; 114(3): 449-58. https://dx.doi.org/10.1160/TH14-12-1067.
  30. Kim S.J., Davis R.P., Jenne C.N. Platelets as modulators of inflammation. Semin. Thromb. Hemost. 2018; 44(2): 91-101.https://dx.doi.org/10.1055/ s-0037-1607432.
  31. Groom K.M., David A.L. The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction. Am. J. Obstet. Gynecol. 2018; 218(Suppl. 2): S829-40. https://dx.doi.org/10.1016/j.ajog.2017.11.565.
  32. Database «Kyoto Encyclopedia of Genes and Genome» (KEGG). Available at: https://www.genome.jp/kegg-bin/show_pathway?hsa04141.
  33. de Bont C.M., Boelens W.C., Pruijn G.J.M. NETosis, complement, and coagulation: a triangular relationship. Cell. Mol. Immunol. 2019; 16(1): 19-27. https://dx.doi.org/10.1038/s41423-018-0024-0.
  34. Jorch S.K., Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat. Med. 2017; 23(3): 279-87. https://dx.doi.org/ 10.1038/nm.4294.
  35. Garovic V.D., White W.M., Vaughan L., Saiki M., Parashuram S., Garcia-Valencia O. et al. Incidence and long-term outcomes of hypertensive disorders of pregnancy. J. Am. Coll. Cardiol. 2020; 75(18): 2323-34. https://dx.doi.org/6/ j.jacc.2020.03.028.
  36. Li Y.Y., Cao J., Li J.L., Zhu J.Y., Li Y.M., Wang D.P. et al. Screening high-risk population of persistent postpartum hypertension in women with preeclampsia using latent class cluster analysis. BMC Pregnancy Childbirth. 2022; 22(1): 687. https://dx.doi.org/10.1186/s12884-022-05003-4.
  37. Manousopoulou A., Abad F.S., Garay-Baquero D.J., Birch B.R., van Rijn B.B., Lwaleed B.A. et al. Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case-control plasma proteomics study. Nutr. Diabetes. 2020; 10(1): 2. https://dx.doi.org/10.1038/s41387-019-0105-x.
  38. Wu P., Kwok C.S., Haththotuwa R., Kotronias R.A., Babu A., Fryer A.A. et al. Pre-eclampsia is associated with a twofold increase in diabetes: a systematic review and meta-analysis. Diabetologia. 2016; 59(12): 2518-26. https://dx.doi.org/10.1007/s00125-016-4098-x.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Volcano diagram for quantified plasma proteins of pregnant women in normal and preeclampsia.

Download (198KB)
Indexing metadata
3. Fig. 2. Biological processes revealed by cluster analysis of differentially represented proteins in plasma in pregnant women in normal and preeclampsia (https://david.ncifcrf.gov/): A, clusters of proteins with significantly elevated levels in preeclampsia; B, clusters of proteins with significantly decreased levels in preeclampsia

Download (504KB)
Indexing metadata

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies