| A Role for miR-145 in Pulmonary Arterial Hypertension. | |
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MedLine Citation:
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PMID: 22715469 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rationale:Despite improved understanding of the underlying genetics, pulmonary arterial hypertension (PAH) remains a severe disease. Extensive remodeling of small pulmonary arteries, including proliferation of pulmonary artery smooth muscle cells (PASMCs), characterizes PAH. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to play a role in vascular remodeling.Objective:We assessed the role of miR-145 in PAH.Methods and Results:We localized miR-145 in mouse lung to smooth muscle. Using quantitative PCR, we demonstrated increased expression of miR-145 in wild-type mice exposed to hypoxia. PAH was evaluated in miR-145 knockout and mice treated with anti-miRs via measurement of systolic right ventricular pressure, right ventricular hypertrophy, and percentage of remodeled pulmonary arteries. miR-145 deficiency and anti-miR-mediated reduction resulted in significant protection from the development of PAH. In contrast, miR-143 anti-miR had no effect. Furthermore, we observed upregulation of miR-145 in lung tissue of patients with idiopathic and heritable PAH compared with unaffected control subjects and demonstrated expression of miR-145 in SMC of remodeled vessels from such patients. Finally, we show elevated levels of miR-145 expression in primary PASMCs cultured from patients with BMPR2 mutations and also in the lungs of BMPR2-deficient mice.Conclusions:miR-145 is dysregulated in mouse models of PAH. Downregulation of miR-145 protects against the development of PAH. In patient samples of heritable PAH and idiopathic PAH, miR-145 is expressed in remodeled vessels and mutations in BMPR2 lead to upregulation of miR-145 in mice and PAH patients. Manipulation of miR-145 may represent a novel strategy in PAH treatment. |
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Authors:
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Paola Caruso; Yvonne Dempsie; Hannah Stevens; Robert A McDonald; Lu Long; Ruifang Lu; Kevin White; Kirsty Mair; John D McClure; Mark Southwood; Paul Upton; Mei Xin; Eva van Rooij; Eric Olson; Nicholas W Morrell; Margaret R Maclean; Andrew H Baker |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-6-19 |
Journal Detail:
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Title: Circulation research Volume: - ISSN: 1524-4571 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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