Regulation and function of miR-214 in pulmonary arterial hypertension

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

doi:10.1086/685079

Regulation and function of miR-214 in pulmonary arterial hypertension

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

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Abstract / Description of output

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.

Original language	English
Journal	Pulmonary circulation
DOIs	https://doi.org/10.1086/685079
Publication status	Published - 3 Feb 2016

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10.1086/685079Licence: Creative Commons: Attribution (CC-BY)

Stevens et al_Pulm_Circ_2015_Accepted ManuscriptAccepted author manuscript, 7.85 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Laura Denby
- laura.denbyed.acuk
- Deanery of Clinical Sciences - Reader
- Centre for Cardiovascular Science
Person: Academic: Research Active

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@article{de92eb5acb76498a8db66d42196a34a7,

title = "Regulation and function of miR-214 in pulmonary arterial hypertension",

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.",

author = "Hannah Stevens and Lin Deng and Grant, {Jennifer S.} and Karine Pinel and Thomas, {Matthew B.} and Morrell, {Nicholas W} and MacLean, {Margaret R.} and Baker, {Andrew H.} and Laura Denby",

year = "2016",

month = feb,

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doi = "10.1086/685079",

language = "English",

journal = "Pulmonary circulation",

issn = "2045-8932",

publisher = "University of Chicago Press",

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TY - JOUR

T1 - Regulation and function of miR-214 in pulmonary arterial hypertension

AU - Stevens, Hannah

AU - Deng, Lin

AU - Grant, Jennifer S.

AU - Pinel, Karine

AU - Thomas, Matthew B.

AU - Morrell, Nicholas W

AU - MacLean, Margaret R.

AU - Baker, Andrew H.

AU - Denby, Laura

PY - 2016/2/3

Y1 - 2016/2/3

N2 - 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.

AB - 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.

U2 - 10.1086/685079

DO - 10.1086/685079

M3 - Article

SN - 2045-8932

JO - Pulmonary circulation

JF - Pulmonary circulation

ER -

Regulation and function of miR-214 in pulmonary arterial hypertension

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Laura Denby

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