title: MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Carr
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barrese
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Stott
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Oleksandr V
authors.initials: OV
authors.lastname: Povstyan
authors.affiliation: Ion Channels Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jepps
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Hericka B
authors.initials: HB
authors.lastname: Figueiredo
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Dongling
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Jamshidi
authors.affiliation: Vascular Research Centre, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.|Ion Channels Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Iain A
authors.initials: IA
authors.lastname: Greenwood