The role of circulating microRNA-181a in the development of preeclampsia associated with chronic arterial hypertension
https://doi.org/10.69964/BMCC-2025-2-4-10-18
Abstract
Relevance. According to research data, up to 8.2% of women enter gestation with pre-existing arterial hypertension (AH), and one third of women have hypertension for the first time before 20 weeks of pregnancy.
The purpose of the study. To study the expression level of microRNA-181a in blood plasma in the first trimester of pregnancy in patients with chronic arterial hypertension (CAH) without preeclampsia, women with CAH-associated preeclampsia (NPE) and pregnant women without a history of hypertension with normotensive pregnancy.
Materials and methods. The study included 130 patients: group 1 (n=58) consisted of pregnant women with CAH without preeclampsia, group 2 (n=42) included women with NPE, and group 3 (n=30) included healthy pregnant women. The expression level of microRNA-181a in blood plasma was assessed in the studied groups at 12-14 weeks gestation using quantitative polymerase chain reaction in real time. Statistical data processing was performed using the IBM SPSS Statistics licensed software package (version 26.0, USA).
Results. Multidirectional changes in the expression level of microRNA-181a were revealed in the study groups: a significant decrease in the expression level of microRNA-181a in the group of patients with NPE compared to women with isolated CAH (p1-2 <0.001) and with healthy pregnant women (p2-3=0.004) and an increased expression level in patients with CAH without PE compared to with the NPE group (p1-2<0.001) and normotensive pregnant women (p1-3=0.011).
Conclusion. microRNA-181a in the first trimester of pregnancy has the potential of aprognostic noninvasive marker of the development of NPE. Further research is required to study the possible mechanisms of the effect of microRNA-181a on the pathogenesis of NPE.
About the Authors
Yu. A. SemenovRussian Federation
Yuri A. Semenov - Doctor of Medical Sciences, Associate Professor, Honored Doctor of the Russian Federation, Director
st. Repina, 1, Ekaterinburg, 620028
Phone: + 7 (343) 371-87-68
V. N. Antonov
Russian Federation
Vladimir N. Antonov - Doctor of Medical Sciences, Associate Professor, Professor of the Therapy Department of the Institute of Continuing Professional Education
st. Vorovskogo, 64, Chelyabinsk, 454092
Phone: + 7 (919) 357-04-73
E. A. Azarenkova
Russian Federation
Evgenia A. Azarenkova - Head of the educational and methodological Department
st. Repina, 1, Ekaterinburg, 620028
Phone: +7 (908) 581-51-86
References
1. Preeclampsia. Eclampsia. Edema, proteinuria, and hypertensive disorders during pregnancy, childbirth, and the postpartum period: clinical guidelines. — Russian Society of Obstetricians and Gynecologists, 2024. https://cr.minzdrav.gov.ru/preview-cr/637_2 (accessed 08/12/2025) (In Russ).
2. Sweeney LC, Lundsberg LS, Culhane JF, Partridge C, Son M. Co-existing chronic hypertension and hypertensive disorders of pregnancy and associated adverse pregnancy outcomes. J Matern Fetal Neonatal Med. 2024;37(1):2305675. https://doi.org/10.1080/14767058.2024.2305675
3. Sousa MG, Lopes RGC, Rocha MLTLFD, Lippi UG, Costa ES, Santos CMPD. Epidemiology of artherial hypertension in pregnants. Einstein ( Sao Paulo). 2019;18:eAO4682. https://doi.org/10.31744/einstein_journal/2020AO4682
4. ACOG Practice Bulletin No. 203. Chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26–e50. https://doi.org/10.1097/aog.0000000000003020
5. Dimitriadis E, Rolnik DL, Zhou W, Estrada-Gutierrez G, Koga K, Francisco RPV, Whitehead C, Hyett J, da Silva Costa F, Nicolaides K, Menkhorst E. Pre-eclampsia. Nat Rev Dis Primers. 2023;9(1):8. https://doi.org/10.1038/s41572-023-00417-6
6. Dolgushina V.F., Chulkov V.S., Vereina N.K., Sinitsyn S.P. Evaluation of the relationship of clinical and genetic factors with complications and pregnancy outcomes in women with preeclampsia on the background of chronic arterial hypertension. Russian Bulletin of the obstetrician-gynecologist. 2014; 14(6):4-8. (In Russ)
7. Moiseeva I.Е. Hypertension in pregnancy in general practice. Russian Family Doctor.2019;23 (2):15-20. https://doi.org/10.17816/RFD2019215-20 (In Russ)
8. Casagrande L, Rezende GP, Guida JP, Costa RS, Parpinelli MA, Surita FG, Costa ML. Maternal and perinatal outcomes related to superimposed pre-eclampsia in a Brazilian cohort of women with chronic hypertension. J Gynaecol Obstet. 2020;149(2):148-153. https://doi.org/10.1002/ijgo.13114
9. Cai M, Kolluru GK, Ahmed A. Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications. J Pregnancy. 2017;2017:6972732. https://doi.org/10.1155/2017/6972732
10. Yang H., Ma Q., Wang Y. et al. Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities. J Transl Med. 2020;18: 32. https://doi.org/10.1186/s12967-020-02227-w
11. Nikitina N.A., Sidorova I.S., Raigorodskaya M.P., Morozova E.A., Timofeev S.A., Ageev M.B., Amiraslanova N.I. Epigenetic mechanisms of preeclampsia development: the role of plasma microRNAs. V.F. Snegirev Archive of Obstetrics and Gynecology. 2024;11(2):179-192. (In Russ) https://doi.org/10.17816/aog623622
12. Hayder H, O’Brien J, Nadeem U, Peng C. MicroRNAs: crucial regulators of placental development. Reproduction. 2018;155(6):259–71. doi: https://doi.org/10.1530/REP-17-0603
13. Kametas NA., Nzelu D., Nicolaides KH. Chronic hypertension and superimposed preeclampsia: screening and diagnosis. Am J Obstet Gynecol. 2022; 226(2S): S1182-1195. https://doi.org/10.1016/j.ajog.2020.11.029
14. Semenov Yu.A., Kazachkov E.L., Veryaskina Yu.A., Chizhovskaya A.V. MicroRNA expression profile in the blood plasma of pregnant women with high and low risk of spontaneous preterm birth and perinatal loss. South Ural Medical Journal. 2021; 2: 18-23. (in Russian)
15. Jung E, Romero R, Yeo L, et al. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226(2s):S844–S866. https://doi.org/10.1016/j.ajog.2021.11.1356
16. Lumbers ER, Delforce SJ, Arthurs AL, Pringle KG. Causes and Consequences of the Dysregulated Maternal Renin-Angiotensin System in Preeclampsia. Front Endocrinol (Lausanne). 2019;10:563. doi: https://doi.org/10.3389/fendo.2019.00563
17. Lumbers ER, Pringle KG. Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy. Am J Physiol Regul Integr Comp Physiol. 2014;306(2): 91-101. https://doi.org/10.1152/ajpregu.00034.2013
18. Marques FZ, Romaine SP, Denniff M, Eales J, Dormer J, Garrelds IM, Wojnar L, Musialik K, Duda-Raszewska B, Kiszka B, Duda M, Morris BJ, Samani NJ, Danser AJ, Bogdanski P, Zukowska-Szczechowska E, Charchar FJ, Tomaszewski M. Signatures of miR-181a on the Renal Transcriptome and Blood Pressure. Mol Med. 2015;21(1):739-748. doi: https://doi.org/10.2119/molmed.2015.00096
19. Kroesen BJ, Teteloshvili N, Smigielska-Czepiel K, Brouwer E, Boots AM, van den Berg A, Kluiver J. Immuno-miRs: critical regulators of T-cell development, function and ageing. Immunology. 2015;144(1):1-10. doi: https://doi.org/10.1111/imm.12367
20. Xie W, Li M, Xu N, Lv Q, Huang N, He J, Zhang Y. MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS One. 2013;8(3):e58639. https://doi.org/10.1371/journal.pone.0058639
21. Norlander AE, Madhur MS. Inflammatory cytokines regulate renal sodium transporters: how, where, and why? Am J Physiol Renal Physiol. 2017;313:F141–F144. https://doi.org/10.1152/ajprenal.00465.2016
22. Rippo MR, Olivieri F, Monsurrò V, Prattichizzo F, Albertini MC, Procopio AD. MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR- 34a and miR-146a. Exp Gerontol. 2014;56:154-63. doi: https://doi.org/10.1016/j.exger.2014.03.002
23. Das S, Kohr M, Dunkerly-Eyring B, Lee DI, Bedja D, Kent OA, Leung AK, Henao-Mejia J, Flavell RA, Steenbergen C. Divergent effects of miR-181 family members on myocardial function through protective cytosolic and detrimental mitochondrial microRNA targets. J Am Heart Assoc. 2017;6:e004694. https://doi.org/10.1161/JAHA.116.004694
24. Garg A, Foinquinos A, Jung M, Janssen-Peters H, Biss S, Bauersachs J, Gupta SK, Thum T. miRNA-181a is a novel regulator of aldosterone-mineralocorticoid receptor-mediated cardiac remodelling. Eur J Heart Fail. 2020;22:1366–1377. https://doi.org/10.1002/ejhf.1813
25. Koushki M, Amiri-Dashatan N, Khodadadi M, Masnavi E, Doustimotlagh AH. The potential predictive value of miR-181 in women with preeclampsia: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2025;25(1):474. https://doi.org/10.1186/s12884-025-07589-x
26. Hromadnikova I, Kotlabova K, Krofta L. Cardiovascular Disease-Associated MicroRNA Dysregulation during the First Trimester of Gestation in Women with Chronic Hypertension and Normotensive Women Subsequently Developing Gestational Hypertension or Preeclampsia with or without Fetal Growth Restriction. Biomedicines. 2022;10(2):256. https://doi.org/10.3390/biomedicines10020256
27. Lin W, Teng SW, Lin TY, Lovel R, Sung HY, Chang WY, Wu TB, Chen HY, Wang LM, Shaw SW. Combinatorial Analysis of Circulating Biomarkers and Maternal Characteristics for Preeclampsia Prediction in the First and Third Trimesters in Asia. Diagnostics (Basel). 2022;12(7):1533. https://doi.org/10.3390/diagnostics12071533
28. Nikitina N.A., Sidorova I.S., Raigorodskaya M.P., Morozova E.A., Timofeev S.A., Ageev M.B., Amiraslanova N.I. Role of microRNAs associated with cardiovascular disease and placental abnormalities in the development of pre-eclampsia. Vopr. ginekol. akus. perinatol. (Gynecology, Obstetrics and Perinatology). 2025; 24(2): 5–19. (In Russian). https://doi.org/10.20953/1726-1678-2025-2-5-19
Review
For citations:
Semenov Yu.A., Antonov V.N., Azarenkova E.A. The role of circulating microRNA-181a in the development of preeclampsia associated with chronic arterial hypertension. Bulletin of maternal and child care. 2025;2(4):10-18. (In Russ.) https://doi.org/10.69964/BMCC-2025-2-4-10-18