Substantial dysregulation of miRNA passenger strands underlies the vascular response to injury

Pinel, K., Diver, L. A., White, K., McDonald, R. A. and Baker, A. H. (2019) Substantial dysregulation of miRNA passenger strands underlies the vascular response to injury. Cells, 8(2), 83. (doi: 10.3390/cells8020083) (PMID:30678104) (PMCID:PMC6406808)

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Abstract

Vascular smooth muscle cell (VSMC) dedifferentiation is a common feature of vascular disorders leading to pro-migratory and proliferative phenotypes, a process induced through growth factor and cytokine signaling cascades. Recently, many studies have demonstrated that small non-coding RNAs (miRNAs) can induce phenotypic effects on VSMCs in response to vessel injury. However, most studies have focused on the contribution of individual miRNAs. Our study aimed to conduct a detailed and unbiased analysis of both guide and passenger miRNA expression in vascular cells in vitro and disease models in vivo. We analyzed 100 miRNA stem loops by TaqMan Low Density Array (TLDA) from primary VSMCs in vitro. Intriguingly, we found that a larger proportion of the passenger strands was significantly dysregulated compared to the guide strands after exposure to pathological stimuli, such as platelet-derived growth factor (PDGF) and IL-1α. Similar findings were observed in response to injury in porcine vein grafts and stent models in vivo. In these studies, we reveal that the miRNA passenger strands are predominantly dysregulated in response to vascular injury.

Item Type:Articles
Keywords:Biomarker, miRNA expression and regulation, passenger miRNA, porcine vein graft and stent models, smooth muscle cells, vascular injury.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and White, Miss Katie and Pinel, Dr Karine and McDonald, Dr Robert and Diver, Miss Louise
Creator Roles:
Pinel, K.Conceptualization, Methodology, Investigation, Formal analysis, Writing – original draft, Writing – review and editing
McDonald, R. A.Conceptualization, Methodology
Baker, A. H.Conceptualization, Writing – original draft, Writing – review and editing, Funding acquisition
Diver, L. A.Methodology
White, K.Methodology
Authors: Pinel, K., Diver, L. A., White, K., McDonald, R. A., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cells
Publisher:MDPI
ISSN:2073-4409
ISSN (Online):2073-4409
Published Online:23 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Cells 8(2): 83
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
162591Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915Institute of Cardiovascular & Medical Sciences
169623Role of non-coding RNA in vascular pathologyAndrew BakerBritish Heart Foundation (BHF)RG/14/3/30706Institute of Cardiovascular & Medical Sciences