Grant, J. S., Morecroft, I., Dempsie, Y., van Rooij, E., MacLean, M. R. and Baker, A. H. (2013) Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension. Pulmonary Circulation, 3(4), pp. 840-850. (doi: 10.1086/674751) (PMID:25006399) (PMCID:PMC4070830)
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Abstract
<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p>
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | MacLean, Professor Margaret and Baker, Professor Andrew and Dempsie, Dr Yvonne and Morecroft, Dr Ian |
Authors: | Grant, J. S., Morecroft, I., Dempsie, Y., van Rooij, E., MacLean, M. R., and Baker, A. H. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Pulmonary Circulation |
Publisher: | Medknow Publications |
ISSN: | 2045-8932 |
ISSN (Online): | 2045-8940 |
Copyright Holders: | Copyright © 2013 Medknow Publications |
First Published: | First published in Pulmonary Circulation 3(4):840-850 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher. |
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