Aspirin Reverses Placental Gene Expression Changes Associated With Preeclampsia

Aspirin is the only medication recommended for preventing preeclampsia, a hypertensive disorder of pregnancy. However, the mechanism(s) by which aspirin prevents preeclampsia are unknown. To better understand the mechanism by which aspirin prevents preeclampsia, we compared expression of genes involved in signal transduction, cardiac remodeling, ion transport, stress and immune response, apoptosis, sarcomere structure, transcriptional regulation, and cell cycle regulation between placental tissues from 4 different cohorts: preeclamptic women, preeclamptic women who took aspirin during pregnancy, non-preeclamptic women, and non-preeclamptic women who took aspirin (N=3 per cohort). Tissues were obtained from the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784). When comparing whole thickness samples, 27 genes had a greater than 5-fold change in expression in the tissues of women with preeclampsia compared to those without. For example, CDKN1B whose protein inhibits the cell cycle, is increased in preeclampsia (-3.7ΔΔCt, 13.4-fold increase). However, in women who took aspirin, both those that developed preeclampsia and those who did not, CDKN1B expression was similar to women without preeclampsia who did not take aspirin indicating a decrease in gene expression in response to aspirin. However, aspirin also increases expression of several genes associated with preeclampsia. For example, we identified that RGS2 and PLAC1 in the decidual layer of the placenta were increased in response to aspirin. Decreases in expression of both genes is associated with preeclampsia. However, 19 genes whose expression is increased in preeclampsia compared to controls had no response to aspirin. Identifying specific genes and pathways that serve as targets of aspirin during pregnancy provides valuable insight into the mechanisms by which aspirin reduces the occurrence of preeclampsia and may help to identify who would benefit most from its use. Additionally, it may identify targets for the development of other preeclampsia preventative or therapeutic medications.