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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Georgina Carr
  • Vincenzo Barrese
  • Jennifer B Stott
  • Oleksandr V Povstyan
  • Jepps, Thomas Andrew Qvistgaard
  • Hericka B Figueiredo
  • Dongling Zheng
  • Yalda Jamshidi
  • Iain A Greenwood

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.

Original languageEnglish
JournalCardiovascular Research
Pages (from-to)581-589
Number of pages9
Publication statusPublished - 7 Jul 2016

Number of downloads are based on statistics from Google Scholar and www.ku.dk

No data available

ID: 167175446