Epigenetic mechanisms of preeclampsia: Role of plasma microRNAs

Abstract

BACKGROUND: Despite the retentive relevance of preeclampsia (PE) among the main causes of maternal morbidity and mortality, its etiology remains unclear. Despite gaps in its pathophysiology, highly effective methods of prognosis, prevention, and treatment are still not devised yet. In recent years, the use of microRNA molecules that epigenetically control the expression of target genes at the post-transcriptional level received great interest as are they of key importance in the proliferation, differentiation, invasion, migration, and apoptosis of trophoblast cells and regulation of angiogenesis, immune response, and other processes during pregnancy AIM: This study aimed to investigate the epigenetic mechanisms of PE development based on the evaluation of the expression of pathogenetically significant microRNAs in women’s blood plasma. MATERIALS AND METHODS: The study included 62 female patients divided into the main study group (n=42 with PE) and the control group (n = 20 healthy women with uncomplicated pregnancy, childbirth, and post-natal period). All patients have undergone general clinical, laboratory, and instrumental examinations. The expression levels of 15 microRNAs in the blood plasma were evaluated using a quantitative real-time polymerase chain reaction. DIANA miRPath v. 3.0 was used to evaluate the effect of differentially expressed microRNAs on the functioning of signaling pathways. Statistical data analyses were performed using Statistica 6.0. RESULTS: Multidirectional changes in the expression levels of 13 of 15 plasma microRNAs were found in the PE group compared with the control group; however, the expression levels of the following eight microRNAs decreased significantly: hsa-miR-146a-5p (p=0.011), hsa-miR-181a-5p (p=0.015), hsa-miR-210-3p (p=0.031), hsa-miR-517a-3p (p=0.004), hsa-miR-517c-3p (p=0.007), hsa-miR-574-3p (p=0.048), hsa-miR-574-5p (p=0.003), and hsa-miR-1304-5p (p=0.001). The expression levels of hsa-miR-20a-5p (FC=0.39; p=0.049) and hsa-miR-143-3p (FC=0.71, p=0.05) significantly decreased in pregnant women with PE and symptoms of fetal growth retardation (FGR) compared with the subgroup without FGR. No significant differences in the expression level of the analyzed microRNAs were found between the subgroups with moderate and severe PE and early and late PE. The functional evaluation of differentially expressed microRNAs among women with PE, considering the identification of their potential target genes, revealed the dysregulation of 40 signaling pathways and biological processes in which these molecules are involved. CONCLUSION: PE progresses alongside significant epigenetic changes accompanied by changes in the microRNA expression profile, which are associated with cardiovascular and cerebrovascular diseases and placental disorders. The detected differentially expressed microRNAs may be potential diagnostic markers of PE.