The role of mir-29a, mir-181a, and mir-222 in preeclamptic and gestational hypertensive patients.

Abstract

Backgrounds Hypertensive disorders of pregnancy, a major cause of maternal and neonatal morbidity worldwide are characterized by widespread maternal endothelial dysfunction and metabolic disorders (blood pressure and insulin resistance). Dysregulation in proteins (AKT and PI3K) involved in the insulin signaling pathway lead to insulin resistance, which is a common feature in the second half of most pregnancies complicated by preeclampsia and gestational hypertension. The objective of this study was to quantify microRNAs in serum and placental tissue of women with gestational hypertension (GH) and preeclampsia (PE). Methods This study is a prospective cross-sectional study involving 32 normotensive pregnant women (control), 32 women with preeclampsia (PE) and 28 with gestational hypertension (GH). The patients were recruited from a regional hospital in Durban, KwaZulu-Natal Province, South Africa. Serum and placental microRNA were quantified using RT-qPCR to compare levels of expression in the control, PE, and GH. In addition, a western blot analysis was carried out to investigate the levels of protein expression (AKT and PI3K) in the insulin signaling pathway. Results Serum, miRNA-222 quantitative real-time PCR expression levels were significantly lower in PE compared to normotensives (p=0.0186). miR-29 expression levels were significantly higher in PE (p<0.0001) and GH (p<0.0001) groups compared to normotensives. miR-181a serum expression levels of GH were significantly higher compared to normotensives (p=0.0070). Placental tissue expression showed significantly higher expression levels of miR-181a in PE (p=0.0344) and GH (p=0.0344) groups compared to normal controls. Western blot analysis of proteins showed a lower expression of AKT-serine and threonine in the PE (p=0.0001) compared to the normal control groups and significantly higher expression in the GH (p=0.0001) groups compared to the normal controls. Furthermore, the expression of the phosphatidyl-inositol-3 kinase (PI3K) was statistically lower in PE (p=0.0001) and GH (p=0.0001) compared to the normal controls. Discussion/Conclusion MicroRNAs may be used as potential biomarkers for PE and GH. The results of this study showed a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the existence of metabolic dysregulation in PE and GH