Circulating miR-206 and Wnt-signaling are associated with cardiovascular complications and a history of preeclampsia in women

Schlosser, K., Kaur, A., Dayan, N., Stewart, D. J., Pilote, L. and Delles, C. (2020) Circulating miR-206 and Wnt-signaling are associated with cardiovascular complications and a history of preeclampsia in women. Clinical Science, 134(2), pp. 87-101. (doi: 10.1042/CS20190920) (PMID:31899480)

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Abstract

Women with a history of preeclampsia (PE) have increased risk of cardiovascular disease (CVD) later in life. However, the molecular determinants underlying this risk remain unclear. We sought to understand how circulating miRNA levels are impacted by prior PE, and relate to biological pathways underpinning cardiovascular disease. RNA sequencing was used to profile plasma levels of 2578 miRNAs in a retrospective study of women with a history of PE or normotensive pregnancy, in two independent cohorts with either acute coronary syndrome (ACS) (n=17-18/group) or no ACS (n=20/group). Differential miRNA alterations were assessed in relation to a history of PE (within each cohort) or ACS (across cohorts), and compared to miRNAs previously reported to be altered during PE. A history of PE was associated with altered levels of 30 and 20 miRNAs in the ACS and non-ACS cohorts, respectively, whereas ACS exposure was associated with alterations in 259 miRNAs. MiR-206 was identified at the intersection of all comparisons relating to past/current PE and ACS exposure, and has previously been implicated in atherogenic activities related to hepatocytes, vascular smooth muscle cells and macrophages. Integration of all differentially altered miRNAs with their predicted and experimentally-validated targets in silico revealed a number of highly targeted genes with potential atherogenic functions (including NFAT5, CCND2 and SMAD2), and one significantly enriched KEGG biological pathway (Wnt signaling) that was shared between all exposure groups. This study provides novel insights into miRNAs, target genes and biological pathways that may underlie the long term cardiovascular sequelae of PE.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Delles, Professor Christian
Authors: Schlosser, K., Kaur, A., Dayan, N., Stewart, D. J., Pilote, L., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:03 January 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Clinical Science 134(4):87-101
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
166900Cardiovascular consequences of preeclampsia in women from the Generation Scotland: Scottish Family Health Study.Christian DellesChief Scientist Office (CSO)ETM/196Institute of Cardiovascular & Medical Sciences