Circulating miRNAs Associated with Dysregulated Vascular and Trophoblast Function as Target-Based Diagnostic Biomarkers for Preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder associated with hypertension and proteinuria. Since there is no proven method to treat PE, early prediction and accurate diagnosis are essential for appropriate management of the disease. Thus, reliable biomarkers for diagnosing PE need to be identified and evaluated. We analyzed serum-soluble factors and miRNAs in 92 patients with PE and an equal number of healthy controls to identify new useful biomarkers for PE. Serum miR-31-5p, miR-155-5p, and miR-214-3p levels were significantly elevated in these patients and highly correlated with clinical symptoms of hypertension and proteinuria, whereas the miR-1290-3p level was decreased. The increased miRNAs were upregulated in an NF-κB-dependent manner and suppressed endothelial nitric oxide synthase (eNOS) and placental growth factor (PlGF) expression. The level of each miRNA had greater than 90% diagnostic accuracy, which was further increased by analyzing its ratio relative to that of miR-1290-3p. Taken together, the ratios of miR-31-5p, miR-155-5p, or miR-214-3p to miR-1290-3p may serve as reliable diagnostic or prognostic tools for PE, thereby providing evidence that these miRNAs are promising mechanism-based targets for designing therapeutic and preventive strategies for the clinical management of PE.

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

“…Thus, the three isoforms of NOS, including iNOS, nNOS and eNOS, are all produced by first trimester trophoblast cells. In addition, we discovered that the expression of all the three NOS isoforms, including iNOS, was suppressed by hydrogen peroxide incubation in TEV-1 cells, which is not consistent with a previous report showing that the serum iNOS levels were increased in PE patients ( Kim et al, 2020 ). We hypothesis that the inconsistence could be due to the complicated cellular pathways functioning during PE progression in patients, since iNOS expression is also regulated by other molecules such as Tumor Necrosis Factor-α (TNF-α) that is stimulated in PE ( Kim et al, 2020 ).…”

Increased Circulating miR-155 identifies a subtype of preeclamptic patients

“…Unlike previous studies [23, 26], in this study, we applied the case-control study and longitudinal study, in which the subjects from both studies were independent. Through the case-control study with a large sample size, we observed that about 30% preeclamptic patients presented high sero-miR-155 level and through longitudinal study we not only found the similar proportion of preeclamptic patients with high sero-miR-155 but also observed that the increase of miR-155 level took place as early as at GW11-13 +6 and maintaining high level across pregnancy, suggesting that certain proportion of preeclamptic patients with high sero-miR-155 level indeed existed and miR-155 was not fit for an uniform predictor for preeclampsia.…”

MiR-1290: a potential therapeutic target for regenerative medicine or diagnosis and treatment of non-malignant diseases

“…The interaction between the uterus and the embryo is vital for the successful implantation and development of the embryo during pregnancy. Endometrial tissue biopsy in cows before implantation of embryos at days 3 and 7 of the estrous cycle (similar to the human menstrual cycle) showed that the expression of several miRNAs changed during this period so that the expression of miR-1290 increased up to 10-fold on day 7 of the estrous cycle under normal conditions [49]. Therefore, more studies are needed on human samples to determine whether the expression of miR-1290 is important for embryo implantation and normal pregnancy.…”