Regulation and function of miR-214 in pulmonary arterial hypertension

Hannah C. Stevens, Lin Deng, Jennifer S. Grant, Karine Pinel, Matthew Thomas, Nicholas W. Morrell, Margaret R. MacLean, Andrew H. Baker, Laura Denby

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Abstract

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 β 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.

Original languageEnglish
Pages (from-to)109-117
Number of pages9
JournalPulmonary Circulation
Volume6
Issue number1
DOIs
Publication statusPublished - 1 Mar 2016

Fingerprint

MicroRNAs
Pulmonary Hypertension
Heart Ventricles
Hypertrophy
Transforming Growth Factors
Phosphoric Monoester Hydrolases
Pulmonary Artery
Smooth Muscle Myocytes
Heart Failure
Blood Pressure
Lung
Mouse Mirn214 microRNA
Hypoxia

Keywords

  • microRNA-199
  • right ventricular hypertrophy
  • sugen 5416 hypoxia model
  • transforming growth factor β 1

Cite this

Stevens, H. C., Deng, L., Grant, J. S., Pinel, K., Thomas, M., Morrell, N. W., ... Denby, L. (2016). Regulation and function of miR-214 in pulmonary arterial hypertension. Pulmonary Circulation, 6(1), 109-117. https://doi.org/10.1086/685079
Stevens, Hannah C. ; Deng, Lin ; Grant, Jennifer S. ; Pinel, Karine ; Thomas, Matthew ; Morrell, Nicholas W. ; MacLean, Margaret R. ; Baker, Andrew H. ; Denby, Laura. / Regulation and function of miR-214 in pulmonary arterial hypertension. In: Pulmonary Circulation. 2016 ; Vol. 6, No. 1. pp. 109-117.
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Stevens, HC, Deng, L, Grant, JS, Pinel, K, Thomas, M, Morrell, NW, MacLean, MR, Baker, AH & Denby, L 2016, 'Regulation and function of miR-214 in pulmonary arterial hypertension', Pulmonary Circulation, vol. 6, no. 1, pp. 109-117. https://doi.org/10.1086/685079

Regulation and function of miR-214 in pulmonary arterial hypertension. / Stevens, Hannah C.; Deng, Lin; Grant, Jennifer S.; Pinel, Karine; Thomas, Matthew; Morrell, Nicholas W.; MacLean, Margaret R.; Baker, Andrew H.; Denby, Laura.

In: Pulmonary Circulation, Vol. 6, No. 1, 01.03.2016, p. 109-117.

Research output: Contribution to journalArticle

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Stevens HC, Deng L, Grant JS, Pinel K, Thomas M, Morrell NW et al. Regulation and function of miR-214 in pulmonary arterial hypertension. Pulmonary Circulation. 2016 Mar 1;6(1):109-117. https://doi.org/10.1086/685079