Abstract 203: Transcriptomic Analysis of Placental Chorionic Villi During Placental Ischemia-induced Hypertension
While the precise etiology of preeclampsia is unclear, it is believed that a central causative agent of the disorder is placental ischemia caused by placental hypoperfusion and chronic ischemia. This results in the secretion of pathogenic factors into the maternal circulation. While a number of these factors have been identified (i.e. sFlt-1, AT1-AA, inflammatory cytokines), the full pathogenic profile remains unresolved. Here we have attempted to identify novel biomarkers and pathogenic factors in the ischemic placenta by quantitative microarray analysis of both mRNA and miRNA expression in a rodent model of chronic placental ischemia, the Reduced Uterine Perfusion Pressure (RUPP) model. Gene expression arrays from chorionic villi from control and RUPP animals (n=6 each) revealed 2557 differentially expressed genes at a statistical cutoff of p<0.05 (1140 up-regulated, 1417 down-regulated. The thirty most differentially affected transcripts had fold changes of 2.6-1.4 and included several genes previously identified in the placenta of human patients and experimental models, including pappalysin-2, CEACAM1, and heme oxygenase-1. Most pronounced was a significant increase in the expression of 9 prolactin family members, indicating a massive upregulation of the prolactin system. In addition, a number of novel pro-inflammatory and anti-angiogenic targets were identified. The expression of miRNA in these samples was also determined, and at a statistical cutoff of p<0.05 there were 577 down-regulated and 458 up-regulated miRNAs, of which 73 were changed by more than 50%. Among the pathways known to be affected by these miRNA’s are the VEGF signaling pathways, HMOX1, the Notch pathway, and the HIF activator p300, all of which have previously been implicated in the etiology of preeclampsia. Functional analysis of these transcripts could provide important mechanistic insight into the regulatory mechanisms behind the development of preeclampsia. Together, these data provide interesting biomarkers for placental ischemia and could suggest new therapeutic targets for the treatment of preeclampsia.
- © 2012 by American Heart Association, Inc.