Differential expression of plasma microRNA in preeclamptic patients at delivery and 1 year postpartum

Am J Obstet Gynecol. 2015 Sep;213(3):367.e1-9. doi: 10.1016/j.ajog.2015.05.013. Epub 2015 May 14.

Abstract

Objective: Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by widespread maternal endothelial dysfunction. Although clinical signs subside following delivery, long-term risks associated with PE include hypertension, stroke, and cardiovascular disease. MicroRNAs (miRNAs) are emerging as critical regulators of biological function, and while alterations to the miRNAome have been described in the context of pregnancy and PE, the postpartum implications of PE on miRNA expression is unknown. The goal of this study was to characterize circulating miRNA profiles at the time of delivery and at 1 year postpartum for women who did and did not develop PE.

Study design: Using a targeted reverse transcription polymerase chain reaction approach, selected miRNAs putatively involved in the pathophysiology of PE were examined in 17 normotensive control and 13 PE maternal plasma samples at the time of delivery and 1 year postpartum. Ingenuity Pathway Analysis was used to map putative messenger RNA targets of differentially expressed miRNA to global molecular networks based on gene function.

Results: Significant increases (P < .05) in 7 miRNAs with antiangiogenic, inflammatory, and apoptotic functions (miR-98-5p, miR-222-3p, miR-210-3p, miR-155-5p, miR-296-3p, miR-181a-5p, miR-29b-3p) were evident in maternal plasma at the time of severe PE compared to time-matched controls. Plasma samples from individuals who developed mild PE exhibited no changes compared to control samples for the subset of miRNAs analyzed here. Differential expression of plasma miRNA at the time of delivery for women with PE were largely resolved at 1 year postpartum, and reduced expression of only miR-221-3p (P < .05) was evident. Network analysis of putative targets of differentially regulated miRNA identified 11 interacting networks with enrichment for proteins involved in cardiovascular disease, organ system development and function, and cell signaling and interaction.

Conclusion: The systemic effect of PE on maternal systems is evident in the circulating miRNAome with substantial alterations in miRNA expression in women who develop severe PE. In addition we provide novel evidence of disruption to miR-221 expression 1 year postpartum following a pregnancy complicated by PE compared to normotensive time-matched controls, which may allude to persistent inflammation in these women after delivery.

Keywords: cardiovascular risk; microRNA; preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cohort Studies
  • Delivery, Obstetric*
  • Female
  • Gene Expression Profiling
  • Humans
  • Longitudinal Studies
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Postpartum Period*
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • MIRN155 microRNA, human
  • MIRN210 microRNA, human
  • MIRN222 microRNA, human
  • MIRN29 microRNA, human
  • MIRN296 microRNA, human
  • MIRN98 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs