Abstract
Effect of Aspirin on Placental Gene Expression in Preeclampsia
The FASEB journal, Vol.33(S1), pp.865.14-865.14
04/2019
DOI: 10.1096/fasebj.2019.33.1_supplement.865.14
Abstract
Preeclampsia (PreE) is a hypertensive disorder of pregnancy. It is the leading cause of maternal morbidity and mortality in pregnancy. Promisingly, aspirin provides some prevention for preeclampsia. The US Preventative Services Task Force (USPSTF) recommends low‐dose aspirin (81mg/day) as a preventative medication for women at high risk of PreE. However, the mechanism(s) by which aspirin prevents PreE are unknown.
To better understand the mechanism by which aspirin prevents PreE, we compared gene expression of 84 cardiovascular genes involved in signal transduction, cardiac remodeling, ion transport, stress and immune response, apoptosis, sarcomere structure, transcriptional regulation, and cell cycle regulation (Qiagen RT2 Profiler Array) between placental tissues from 4 different cohorts: preeclamptic women, preeclamptic women who took aspirin during pregnancy, nonpreeclamptic women, and non‐preeclamptic women who took aspirin (N=3 per cohort). The placental tissues were obtained from the Maternal Fetal Tissue Bank at the University of Iowa (IRB# 200910784).
We detected that 27 genes had a greater than 5 fold higher expression in the placentas of preeclamptics in comparison to placentas from women without PreE. However, 19 of these genes did not have elevated expression in either of the aspirin groups, even in women who developed PreE while taking aspirin. Further, only 1 gene (NPPB) met the 5 fold threshold when comparing women who developed PreE while on aspirin to women who developed PreE while not on aspirin. In comparing women who did not develop PreE while on aspirin to women without PreE who were not on aspirin, 2 genes were significantly elevated, but did not meet the 5 fold threshold (ACE and ADRA1A); yet, 2 genes were at least 5 fold higher in the group on aspirin (SLC12A1 and THBS1).
To validate our approach, we interrogated a publicly available microarray dataset describing the expression changes in response to treatment with aspirin (GSE76583). Interestingly, others have also demonstrated that ACE, ADRA1A, SLC12A1, and THBS1 are up‐regulated in response to aspirin in primary colorectal carcinoma cells when treated with aspirin ex vivo. Although we have taken a different approach by studying samples from participants who took aspirin for clinical reasons, we identify some of the same targets. Thus, our approach to use patient samples may yield insights into the pathways by which aspirin prevents PreE. At this sample size, significant variability between participants makes the identification of statistically significant challenges difficult, but importantly we were still able to identify numerous genes that had a large change in expression with the use of aspirin. The identification of gene expression changes will be utilized to understand the mechanisms by which aspirin prevents PreE and to design preventative and therapeutic treatments to efficiently target these mechanisms.
Support or Funding Information
The American Physiological Society STRIDE fellowship (BC), The Iowa Center for Research by Undergraduates Fellowship (BC), AHA Postdoctoral Fellowship (SS), AHA Strategically Focused Research Network in Hypertension (MS, JG, SS, DS), and the Swift Family Foundation (DS, ED).
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Effect of Aspirin on Placental Gene Expression in Preeclampsia
- Creators
- Brandon J Cooley - University of IowaSabrina M Scroggins - University of IowaGuorui Deng - University of IowaJustin L Grobe - University of IowaEric J Devor - University of IowaMark K Santillan - University of IowaDonna A Santillan - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.33(S1), pp.865.14-865.14
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2019.33.1_supplement.865.14
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- The American Physiological Society STRIDE AHA Postdoctoral Fellowship The Iowa Center for Research by Undergraduates Fellowship Swift Family Foundation AHA Strategically Focused Research Network in Hypertension
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Neuroscience and Pharmacology; Obstetrics and Gynecology
- Record Identifier
- 9984317107402771
Metrics
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