Regulation and function of miR-214 in pulmonary arterial hypertension

Stevens, H. C., Deng, L., Grant, J. S., Pinel, K., Thomas, M., Morrell, N. W., MacLean, M. R. and Baker, A. (2016) Regulation and function of miR-214 in pulmonary arterial hypertension. Pulmonary Circulation, 6(1), pp. 109-117. (doi: 10.1086/685079) (PMID:27162619) (PMCID:PMC4860547)

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Abstract

Dysregulation of miRNAs can contribute to the aetiology of diseases including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle in mice and rats exposed to the SU 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in PASMCs exposed to TGF-β1 but not BMP4. We then examined miR-214-/- mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in systolic right ventricular pressure or remodelling observed between the miR-214-/- and WT hypoxic groups. However, we observed a significant increase in right ventricular hypertrophy in hypoxic miR-214-/- male mice compared to controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214-/- mice. Thus, miR-214 stem loop loss leads to elevated right ventricular hypertrophy and may contribute to the heart failure associated with PAH.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLean, Professor Margaret and Baker, Professor Andrew and Pinel, Dr Karine and Stevens, Dr Hannah
Authors: Stevens, H. C., Deng, L., Grant, J. S., Pinel, K., Thomas, M., Morrell, N. W., MacLean, M. R., and Baker, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pulmonary Circulation
Publisher:University of Chicago Press
ISSN:2045-8932
ISSN (Online):2045-8940
Published Online:03 February 2016

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
597901Development of MiR145 Antagonism as a novel Therapeutic strategy for Application to the treatment of pulmonary arterial hypertension.Andrew BakerBritish Heart Foundation (BHF)SP/12/9/29593RI CARDIOVASCULAR & MEDICAL SCIENCES
583361BHF Chair of Translational Cardiovascular SciencesAndrew BakerBritish Heart Foundation (BHF)CH/11/2/28733RI CARDIOVASCULAR & MEDICAL SCIENCES