MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension
| Autor: | Carr, G, Barrese, V, Stott, JB, Povstyan, OV, Jepps, TA, Figueiredo, HB, Zheng, D, Jamshidi, Y, Greenwood, IA |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Carr, G, Barrese, V, Stott, J B, Povstyan, O V, Jepps, T A, Figueiredo, H B, Zheng, D, Jamshidi, Y & Greenwood, I A 2016, ' MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension ', Cardiovascular Research, vol. 112, pp. 581-589 . https://doi.org/10.1093/cvr/cvw177 Cardiovascular Research |
| ISSN: | 1755-3245 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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