Role of microRNAs associated with cardiovascular disease and placental abnormalities in the development of pre-eclampsia

Objective. To study the role of microRNAs associated with cardiovascular disease (CVD) and placental abnormalities in the development of pre-eclampsia (PE) based on a comparative analysis of their plasma expression levels in pregnant women with PE, fetal growth restriction (FGR) and in healthy controls. Patients and methods. The study included 74 patients: group I (study group) – 42 pregnant women with PE; group II (comparison group) – 12 pregnant women with FGR; group III (control group) – 20 healthy women with uncomplicated pregnancy and labor. General clinical, laboratory and instrumental methods of investigation were performed, and the expression levels of 15 microRNAs in blood plasma were determined by a real-time PCR: hsa-miR-20a-5p, hsa-miR-143-3p, hsa-miR-146a-5p, hsa-miR-181a-5p, hsa-miR-210-3p, hsa-miR-320a-3p, hsa-miR-375-3p, hsa-miR-517a-3p, hsa-miR-517c-3p, hsamiR-574-3p, hsa-miR-574-5p, hsa-miR-1304-5p, hsa-miR-210-5p, hsa-miR-4498, hsa-miR-1972. Results. The statistically significant differential expression of 8 out of 15 microRNAs was found only in pregnant women with PE (low levels of hsa-miR-146a-5p, hsa-miR-181a-5p, hsa-miR-210-3p, hsa-miR-517a-3p, hsa-miR-517c-3p, hsa-miR-574-3p, hsa-miR-574-5p, hsa-miR-1304-5p). Changes in microRNA levels had a similar unidirectional pattern in all clinical variants of PE (early- and late-onset, moderate and severe, with and without VTE). Bioinformatics analysis showed that the differential expression of 8 microRNAs in PE affects a large number of biological processes and signaling pathways (transcriptional regulation, cell adhesion, cell cycle, cell proliferation and apoptosis, organ and system development, metabolic processes, modulates immune system functions, affects many signaling pathways, including TGF-b, HIF-1, FoxO, Hippo, p53-mediated pathway, etc.). Conclusion. The development of PE, regardless of its clinical phenotype, is accompanied by dysregulation of microRNAs associated with cardiovascular and cerebrovascular diseases, metabolic disorders, inflammation, and involved in many cellular processes (proliferation, invasion, migration, apoptosis, and cell cycle) in trophoblast tissue. Key words: pregnancy, fetal growth restriction (FGR), microRNAs, pre-eclampsia, signaling pathways, trophoblast