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Lookup NU author(s): Dr Jenny Grant
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Dysregulation of microRNAs (miRNAs) can contribute to the etiology 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 (RV) in mice and rats exposed to the Sugen (SU) 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in pulmonary artery smooth muscle cells exposed to transforming growth factor beta 1 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 RV systolic pressure or remodeling observed between the miR-214(-/-) and wild-type hypoxic groups. However, we observed a significant increase in RV hypertrophy (RVH) in hypoxic miR-214(-/-) male mice compared with 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 RVH and may contribute to the heart failure associated with PAH.
Author(s): Stevens HC, Deng L, Grant JS, Pinel K, Thomas M, Morrell NW, MacLean MR, Baker AH, Denby L
Publication type: Article
Publication status: Published
Journal: Pulmonary Circulation
Year: 2016
Volume: 6
Issue: 1
Pages: 109-117
Print publication date: 01/03/2016
Online publication date: 03/02/2016
Acceptance date: 17/11/2015
ISSN (print): 2045-8932
ISSN (electronic): 2045-8940
Publisher: University of Chicago Press
URL: http://dx.doi.org/10.1086/685079
DOI: 10.1086/685079
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