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MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension.

Carr, G; Barrese, V; Stott, JB; Povstyan, OV; Jepps, TA; Figueiredo, HB; Zheng, D; Jamshidi, Y; Greenwood, IA (2016) MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension. Cardiovasc Res, 112 (2). pp. 581-589. ISSN 1755-3245 https://doi.org/10.1093/cvr/cvw177
SGUL Authors: Greenwood, Iain Andrew Jamshidi, Yalda Stott, Jennifer Beth Barrese, Vincenzo

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Abstract

AIMS: Kv7.4, a voltage-dependent potassium channel expressed throughout the vasculature, controls arterial contraction and is compromised in hypertension by an unknown mechanism. MicroRNAs (miRs) are post-transcriptional regulators of protein production and are altered in disease states such as hypertension. We investigated whether miRs regulate Kv7.4 expression. METHODS AND RESULTS: In renal and mesenteric arteries (MAs) of the spontaneously hypertensive rat (SHR), Kv7.4 protein decreased compared with the normotensive (NT) rat without a decrease in KCNQ4 mRNA, inferring that Kv7.4 abundance was determined by post-transcriptional regulation. In silico analysis of the 3' UTR of KCNQ4 revealed seed sequences for miR26a, miR133a, miR200b, miR153, miR214, miR218, and let-7d with quantitative polymerase chain reaction showing miR153 increased in those arteries from SHRs that exhibited decreased Kv7.4 levels. Luciferase reporter assays indicated a direct targeting effect of miR153 on the 3' UTR of KCNQ4. Introduction of high levels of miR153 to MAs increased vascular wall thickening and reduced Kv7.4 expression/Kv7 channel function compared with vessels receiving a non-targeting miR, providing a proof of concept of Kv7.4 regulation by miR153. CONCLUSION: This study is the first to define a role for aberrant miR153 contributing to the hypertensive state through targeting of KCNQ4 in an animal model of hypertension, raising the possibility of the use of miR153-related therapies in vascular disease.

Item Type: Article
Additional Information: Copyright The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Arteries, Hypertension, KCNQ4, Kv7.4, miR153, Arteries, Hypertension, KCNQ4, Kv7.4, miR153, Cardiovascular System & Hematology, 1102 Cardiovascular Medicine And Haematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: Cardiovasc Res
ISSN: 1755-3245
Language: eng
Dates:
DateEvent
7 July 2016Published Online
1 July 2016Accepted
1 November 2016Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MR/K019074/1Medical Research CouncilUNSPECIFIED
PG/12/63/29824British Heart FoundationUNSPECIFIED
PubMed ID: 27389411
Web of Science ID: WOS:000387985300007
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108055
Publisher's version: https://doi.org/10.1093/cvr/cvw177

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