研究子痫前期临床异质性与分子亚型的现代技术手段

封面


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

本综述旨在探讨应用现代技术手段研究子痫前期发病机制的现状。子痫前期是妊娠期间的严重并发症，至今仍在孕产妇和围产期发病率与死亡率构成中占据重要位置。近几十年来，全球科学界在子痫前期的研究，特别是在其发病机制方面，取得了显著进展。已明确氧化应激、内质网应激、线粒体功能障碍、炎症及继发性内皮功能障碍的作用，研究了血管生成与抗血管生成因子、补体蛋白级联反应及凝血系统激活的重要性。尽管如此，至今尚未建立针对该妊娠并发症的高效预测、预防和治疗方法。近年来，人们越来越关注这样一种可能性：子痫前期可能存在多个亚型，其在分子发病机制、病变程度、累及范围以及母体和围产期结局方面各不相同。因此，有必要借助现代创新型高通量技术，对子痫前期的病理生理机制进行更加深入和全面的研究，并在系统层面上同步评估其可能涉及的各类变化。满足上述要求的是利用多种组学平台的大数据技术，包括表观遗传学、基因组学、转录组学、蛋白质组学、代谢组学等。本文分析了已发表研究中对不同临床表型子痫前期孕妇的胎盘组织及体液样本所进行的转录组、蛋白质组和肽组研究成果，结合临床病史和胎盘组织学变异，识别出子痫前期的分子亚型。研究表明，子痫前期的临床异质性源于其分子遗传机制的高度变异性。本文特别关注采用多组学整合分析的研究成果，强调在制定个体化管理策略、精准预测与预防方案，以及决定延长妊娠或提前分娩时，应考虑不同的分子亚型。文章还介绍了利用组学技术进一步研究子痫前期病理生理机制的前景方向。通过积累和分析相关研究结果，有望在潜在生物标志物和分子靶点的基础上，改进该妊娠并发症的诊断、预防和治疗策略。

全文:

受限制的访问

作者简介

Mariia N. Gololobova

I.M. Sechenov First Moscow State Medical University

Email: gololobova.mar@gmail.com
ORCID iD: 0009-0002-9141-8631

Resident

俄罗斯联邦, Moscow

Natalya A. Nikitina

I.M. Sechenov First Moscow State Medical University

Email: natnikitina@list.ru
ORCID iD: 0000-0001-8659-9963
SPIN 代码: 8344-1517

MD, Dr. Sci. (Medicine)

俄罗斯联邦, Moscow

Iraida S. Sidorova

I.M. Sechenov First Moscow State Medical University

Email: sidorovais@yandex.ru
ORCID iD: 0000-0003-2209-8662
SPIN 代码: 3823-8259

Academician of RAS, MD, Dr. Sci. (Medicine)

俄罗斯联邦, Moscow

Mikhail B. Ageev

I.M. Sechenov First Moscow State Medical University

Email: mikhaageev@yandex.ru
ORCID iD: 0000-0002-6603-804X
SPIN 代码: 3122-7420

MD, Cand. Sci. (Medicine), Assistant Lecturer

俄罗斯联邦, Moscow

Nigar I. Amiraslanova

I.M. Sechenov First Moscow State Medical University

编辑信件的主要联系方式.
Email: amiraslanova00@mail.ru
ORCID iD: 0009-0008-7446-3995

Resident

俄罗斯联邦, Moscow

参考

  1. Clinical recommendations: Preeclampsia. Eclampsia. Edema, proteinuria and hypertensive disorders during pregnancy, childbirth and the postpartum period (05.09.2024). Approved by the Ministry of Health of the Russian Federation. Moscow; 2024. (In Russ.)
  2. Dimitriadis E, Rolnik DL, Zhou W, et al. Pre-eclampsia. Nat Rev Dis Primers. 2023;9(1):8. doi: 10.1038/s41572-023-00417-6
  3. Poon LC, Shennan A, Hyett JA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145(Suppl 1):1–33. doi: 10.1002/ijgo.12802
  4. Maternal mortality [Internet]. Who.int. [cited 2024 Oct 25]. Available from: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality
  5. Pittara T, Vyrides A, Lamnisos D, Giannakou K. Pre-eclampsia and long-term health outcomes for mother and infant: an umbrella review. BJOG. 2021;128(9):1421–1430. doi: 10.1111/1471-0528.16683
  6. Turbeville HR, Sasser JM. Preeclampsia beyond pregnancy: long-term consequences for mother and child. Am J Physiol Renal Physiol. 2020;318(6):F1315–F1326. doi: 10.1152/ajprenal.00071.2020
  7. Magee LA, Brown MA, Hall DR, et al. The 2021 International society for the study of hypertension in pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022;27:148–169. doi: 10.1016/j.preghy.2021.09.008
  8. Roberts JM, Rich-Edwards JW, McElrath TF, et al. Subtypes of preeclampsia: recognition and determining clinical usefulness. Hypertension. 2021;77(5):1430–1441. doi: 10.1161/hypertensionaha.120.14781
  9. Redman CWG, Staff AC, Roberts JM. Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways. Am J Obstet Gynecol. 2022;226(2S):S907–S927. doi: 10.1016/j.ajog.2020.09.047
  10. Staff AC. The two-stage placental model of preeclampsia: An update. J Reprod Immunol. 2019;134–135:1–10. doi: 10.1016/j.jri.2019.07.004
  11. Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019:l2381. doi: 10.1136/bmj.l2381
  12. Hu M, Li J, Baker PN, Tong C. Revisiting preeclampsia: a metabolic disorder of the placenta. FEBS J. 2022;289(2):336–354. doi: 10.1111/febs.15745
  13. Nzelu D, Dumitrascu-Biris D, Nicolaides KH, Kametas NA. Chronic hypertension: first-trimester blood pressure control and likelihood of severe hypertension, preeclampsia, and small for gestational age. Am J Obstet Gynecol. 2018;218(3):337.e1–337.e7. doi: 10.1016/j.ajog.2017.12.235
  14. Panaitescu AM, Syngelaki A, Prodan N, et al. Chronic hypertension and adverse pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol. 2017;50(2):228–235. doi: 10.1002/uog.17493
  15. He B, Huang Z, Huang C, Nice EC. Clinical applications of plasma proteomics and peptidomics: Towards precision medicine. Proteomics Clin Appl. 2022;16(6). doi: 10.1002/prca.202100097
  16. Boroń D, Kornacki J, Gutaj P, et al. Corin — the early marker of preeclampsia in pregestational diabetes mellitus. J Clin Med. 2022;12(1):61. doi: 10.3390/jcm12010061
  17. Kattah A. Preeclampsia and kidney disease: deciphering cause and effect. Curr Hypertens Rep. 2020;22(11):91. doi: 10.1007/s11906-020-01099-1
  18. De Carolis S, Garufi C, Garufi E, et al. Autoimmune congenital heart block: a review of biomarkers and management of pregnancy. Front Pediatr. 2020;8:607515. doi: 10.3389/fped.2020.607515
  19. Esteve-Valverde E, Alijotas-Reig J, Belizna C, et al. Low complement levels are related to poor obstetric outcomes in women with obstetric antiphospholipid syndrome. The EUROAPS Registry Study Group. Placenta. 2023;136:29–34. doi: 10.1016/j.placenta.2023.04.001
  20. Dong Y, Yuan F, Dai Z, et al. Preeclampsia in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis. Clin Rheumatol. 2020;39(2):319–325. doi: 10.1007/s10067-019-04823-8
  21. Jahanyar B, Tabatabaee H, Rowhanimanesh A. Harnessing deep learning for omics in an era of COVID-19. OMICS. 2023;27(4):141–152. doi: 10.1089/omi.2022.0155
  22. Benny PA, Alakwaa FM, Schlueter RJ, et al. A review of omics approaches to study preeclampsia. Placenta. 2020;92:17–27. doi: 10.1016/j.placenta.2020.01.008
  23. Hartmann S, Botha SM, Gray CM, et al. Can single-cell and spatial omics unravel the pathophysiology of pre-eclampsia? J Reprod Immunol. 2023;159:104136. doi: 10.1016/j.jri.2023.104136
  24. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094–1112. doi: 10.1161/circresaha.118.313276
  25. Duhig KE, Myers J, Seed PT, et al. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019;393(10183):1807–1818. doi: 10.1016/s0140-6736(18)33212-4
  26. Zeisler H, Llurba E, Chantraine F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22. doi: 10.1056/nejmoa1414838
  27. Szilagyi A, Gelencser Z, Romero R, et al. Placenta-specific genes, their regulation during villous trophoblast differentiation and dysregulation in preterm preeclampsia. Int J Mol Sci. 2020;21(2):628. doi: 10.3390/ijms21020628
  28. Campbell KA, Colacino JA, Puttabyatappa M, et al. Placental cell type deconvolution reveals that cell proportions drive preeclampsia gene expression differences. Commun Biol. 2023;6(1):264. doi: 10.1038/s42003-023-04623-6
  29. Vennou KE, Kontou PI, Braliou GG, Bagos PG. Meta-analysis of gene expression profiles in preeclampsia. Pregnancy Hypertens. 2020;19:52–60. doi: 10.1016/j.preghy.2019.12.007
  30. Guo F, Zhang B, Yang H, et al. Systemic transcriptome comparison between early- and late-onset pre-eclampsia shows distinct pathology and novel biomarkers. Cell Prolif. 2021;54(2):e12968. doi: 10.1111/cpr.12968
  31. Naydenov D, Vashukova E, Barbitoff Y, et al. Current status and prospects of the single-cell sequencing technologies for revealing the pathogenesis of pregnancy-associated disorders. Genes. 2023;14(3):756. doi: 10.3390/genes14030756
  32. Zhou W, Wang H, Yang Y, et al. Trophoblast cell subtypes and dysfunction in the placenta of individuals with preeclampsia revealed by single-cell RNA sequencing. Mol Cells. 2022;45(5):317–328. doi: 10.14348/molcells.2021.0211
  33. Zhang T, Bian Q, Chen Y, et al. Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single-cell RNA sequencing. Mol Genet Genomic Med. 2021;9(8):e1730. doi: 10.1002/mgg3.1730
  34. Cao J, Jiang W, Yin Z, et al. Mechanistic study of pre-eclampsia and macrophage-associated molecular networks: bioinformatics insights from multiple datasets. Front Genet. 2024;15:1376971. doi: 10.3389/fgene.2024.1376971
  35. Leavey K, Bainbridge SA, Cox BJ. Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia. PLoS One. 2015;10(2):e0116508. doi: 10.1371/journal.pone.0116508
  36. Leavey K, Benton SJ, Grynspan D, et al. Unsupervised placental gene expression profiling identifies clinically relevant subclasses of human preeclampsia. Hypertension. 2016;68(1):137–147. doi: 10.1161/hypertensionaha.116.07293
  37. Benton SJ, Leavey K, Grynspan D, et al. The clinical heterogeneity of preeclampsia is related to both placental gene expression and placental histopathology. Am J Obstet Gynecol. 2018;219(6):604.e1–604.e25. doi: 10.1016/j.ajog.2018.09.036
  38. Gibbs I, Leavey K, Benton SJ, et al. Placental transcriptional and histologic subtypes of normotensive fetal growth restriction are comparable to preeclampsia. Am J Obstet Gynecol. 2019;220(1):110.e1–110.e21. doi: 10.1016/j.ajog.2018.10.003
  39. Horii M, To C, Morey R, et al. Histopathologic and transcriptomic profiling identifies novel trophoblast defects in patients with preeclampsia and maternal vascular malperfusion. Mod Pathol. 2023;36(2):100035. doi: 10.1016/j.modpat.2022.100035
  40. Redline RW, Ravishankar S, Bagby CM, et al. Four major patterns of placental injury: a stepwise guide for understanding and implementing the 2016 Amsterdam consensus. Mod Pathol. 2021;34(6):1074–1092. doi: 10.1038/s41379-021-00747-4
  41. Mateos J, Carneiro I, Corrales F, et al. Multicentric study of the effect of pre-analytical variables in the quality of plasma samples stored in biobanks using different complementary proteomic methods. J Proteomics. 2017;150:109–120. doi: 10.1016/j.jprot.2016.09.003
  42. Whitehead CL, Walker SP, Tong S. Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications: Circulating RNA biomarkers for pregnancy complications. Prenat Diagn. 2016;36(11):997–1008. doi: 10.1002/pd.4934
  43. Rasmussen M, Reddy M, Nolan R, et al. RNA profiles reveal signatures of future health and disease in pregnancy. Nature. 2022;601(7893):422–427. doi: 10.1038/s41586-021-04249-w
  44. Tarca AL, Romero R, Erez O, et al. Maternal whole blood mRNA signatures identify women at risk of early preeclampsia: a longitudinal study. J Matern Fetal Neonatal Med. 2021;34(21):3463–3474. doi: 10.1080/14767058.2019.1685964
  45. Moufarrej MN, Vorperian SK, Wong RJ, et al. Early prediction of preeclampsia in pregnancy with cell-free RNA. Nature. 2022;602(7898):689–694. doi: 10.1038/s41586-022-04410-z
  46. Tambor V, Fučíková A, Lenčo J, et al. Application of proteomics in biomarker discovery: a primer for the clinician. Physiol Res. 2010;59(4):471–497. doi: 10.33549/physiolres.931758
  47. Huang J, Chen X, Fu X, et al. Advances in aptamer-based biomarker discovery. Front Cell Dev Biol. 2021;9:659760. doi: 10.3389/fcell.2021.659760
  48. Li KW, Gonzalez-Lozano MA, Koopmans F, Smit AB. Recent developments in data independent acquisition (DIA) mass spectrometry: application of quantitative analysis of the brain proteome. Front Mol Neurosci. 2020;13:564446. doi: 10.3389/fnmol.2020.564446
  49. Anderson NL, Anderson NG. The human plasma proteome. Mol Cell Proteomics. 2002;1(11):845–867. doi: 10.1074/mcp.r200007-mcp200
  50. Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. TJ Matern Fetal Neonatal Med. 2008;21(1):9–23. doi: 10.1080/14767050701830480
  51. Tarca AL, Romero R, Benshalom-Tirosh N, et al. The prediction of early preeclampsia: Results from a longitudinal proteomics study. PLoS One. 2019;14(6):e0217273. doi: 10.1371/journal.pone.0217273
  52. Korzeniewski SJ, Romero R, Chaiworapongsa T, et al. Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study. Am J Obstet Gynecol. 2016;214(5):629.e1–629.e17. doi: 10.1016/j.ajog.2015.11.015
  53. Brosens I, Pijnenborg R, Vercruysse L, Romero R. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011;204(3):193–201. doi: 10.1016/j.ajog.2010.08.009
  54. Than NG, Posta M, Györffy D, et al. Early pathways, biomarkers, and four distinct molecular subclasses of preeclampsia: the intersection of clinical, pathological, and high-dimensional biology studies. Placenta. 2022;125:10–19. doi: 10.1016/j.placenta.2022.03.009
  55. Erez O, Romero R, Maymon E, et al. The prediction of late-onset preeclampsia: results from a longitudinal proteomics study. PLoS One. 2017;12(7):e0181468. doi: 10.1371/journal.pone.0181468
  56. Stepan H, Hund M, Andraczek T. Combining biomarkers to predict pregnancy complications and redefine preeclampsia: The angiogenic-placental syndrome. Hypertension. 2020;75(4):918–926. doi: 10.1161/hypertensionaha.119.13763
  57. Tarca AL, Taran A, Romero R, et al. Prediction of preeclampsia throughout gestation with maternal characteristics and biophysical and biochemical markers: a longitudinal study. Am J Obstet Gynecol. 2022;226(1):126.e1–126.e22. doi: 10.1016/j.ajog.2021.01.020
  58. Than NG, Romero R, Tarca AL, et al. Integrated systems biology approach identifies novel maternal and placental pathways of preeclampsia. Front Immunol. 2018;9:1661. doi: 10.3389/fimmu.2018.01661
  59. Than NG, Romero R, Györffy D, et al. Molecular subclasses of preeclampsia characterized by a longitudinal maternal proteomics study: distinct biomarkers, disease pathways and options for prevention. J Perinat Med. 2022;51(1):51–68. doi: 10.1515/jpm-2022-0433
  60. Than NG, Romero R, Posta M, et al. Classification of preeclampsia according to molecular clusters with the goal of achieving personalized prevention. J Reprod Immunol. 2024;161:104172. doi: 10.1016/j.jri.2023.104172
  61. Schrader M. Origins, technological development, and applications of peptidomics. In: Methods in Molecular Biology. New York: Springer; 2018:3–39.
  62. Xu Z, Wu C, Xie F, et al. Comprehensive quantitative analysis of ovarian and breast cancer tumor peptidomes. J Proteome Res. 2015;14(1):422–433. doi: 10.1021/pr500840w
  63. Neves LX, Granato DC, Busso-Lopes AF, et al. Peptidomics-driven strategy reveals peptides and predicted proteases associated with oral cancer prognosis. Mol Cell Proteomics 2021;20:100004. doi: 10.1074/mcp.ra120.002227
  64. Checco JW. Identifying and measuring endogenous peptides through peptidomics. ACS Chem Neurosci. 2023;14(20):3728–3731. doi: 10.1021/acschemneuro.3c00546
  65. Krochmal M, Schanstra JP, Mischak H. Urinary peptidomics in kidney disease and drug research. Expert Opin Drug Discov. 2018;13(3):259–268. doi: 10.1080/17460441.2018.1418320
  66. Coelho M, Capela J, Mendes VM, et al. Peptidomics unveils distinct acetylation patterns of histone and annexin A1 in differentiated thyroid cancer. Int J Mol Sci. 2023;25(1):376. doi: 10.3390/ijms25010376
  67. Naryzhny S. Proteomics and Its Applications in Cancers 2.0. Int J Mol Sci. 2024;25(8):4447. doi: 10.3390/ijms25084447
  68. Ives CW, Sinkey R, Rajapreyar I, et al. Preeclampsia — pathophysiology and clinical presentations. J Am Coll Cardiol. 2020;76(14):1690–1702. doi: 10.1016/j.jacc.2020.08.014

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Eco-Vector, 2025


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 86335 от 11.12.2023 г.  
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ЭЛ № ФС 77 - 80633 от 15.03.2021 г.