title: Differential expression of plasma microRNA in preeclamptic patients at delivery and 1 year postpartum.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Malia Su-Qin
authors.initials: MS
authors.lastname: Murphy
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Richard Cary
authors.initials: RC
authors.lastname: Casselman
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Tayade
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Department of Obstetrics and Gynecology, Kingston General Hospital, Kingston, Ontario, Canada. Electronic address: gns@queensu.ca.
authors.forename: Graeme Neil
authors.initials: GN
authors.lastname: Smith
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D036861:Delivery, Obstetric; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008137:Longitudinal Studies; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D049590:Postpartum Period; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D035683:MicroRNAs; C524942:MIRN155 microRNA, human; C543800:MIRN210 microRNA, human; C525710:MIR222, human; C549871:MIRN296 microRNA, human; C532045:MIRN29a microRNA, human; C546084:MIRN98 microRNA, human; C540193:MIrn181 microRNA, human
keywords: cardiovascular risk; microRNA; preeclampsia