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The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension

Human genetic discoveries offer a powerful method to implicate pathways of major importance to disease pathobiology and hence provide targets for pharmacological intervention. The genetics of pulmonary arterial hypertension (PAH) strongly implicates loss-of-function of the bone morphogenetic protein...

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Autores principales: Ormiston, Mark L., Upton, Paul D., Li, Wei, Morrell, Nicholas W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bloomsbury Qatar Foundation Journals 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710869/
https://www.ncbi.nlm.nih.gov/pubmed/26779522
http://dx.doi.org/10.5339/gcsp.2015.47
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author Ormiston, Mark L.
Upton, Paul D.
Li, Wei
Morrell, Nicholas W.
author_facet Ormiston, Mark L.
Upton, Paul D.
Li, Wei
Morrell, Nicholas W.
author_sort Ormiston, Mark L.
collection PubMed
description Human genetic discoveries offer a powerful method to implicate pathways of major importance to disease pathobiology and hence provide targets for pharmacological intervention. The genetics of pulmonary arterial hypertension (PAH) strongly implicates loss-of-function of the bone morphogenetic protein type II receptor (BMPR-II) signalling pathway and moreover implicates the endothelial cell as a central cell type involved in disease initiation. We and others have described several approaches to restore BMPR-II function in genetic and non-genetic forms of PAH. Of these, supplementation of endothelial BMP9/10 signalling with exogenous recombinant ligand has been shown to hold considerable promise as a novel large molecule biopharmaceutical therapy. Here, we describe the mechanism of action and discuss potential additional effects of BMP ligand therapy.
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spelling pubmed-47108692016-01-15 The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension Ormiston, Mark L. Upton, Paul D. Li, Wei Morrell, Nicholas W. Glob Cardiol Sci Pract Mechanisms of Disease Human genetic discoveries offer a powerful method to implicate pathways of major importance to disease pathobiology and hence provide targets for pharmacological intervention. The genetics of pulmonary arterial hypertension (PAH) strongly implicates loss-of-function of the bone morphogenetic protein type II receptor (BMPR-II) signalling pathway and moreover implicates the endothelial cell as a central cell type involved in disease initiation. We and others have described several approaches to restore BMPR-II function in genetic and non-genetic forms of PAH. Of these, supplementation of endothelial BMP9/10 signalling with exogenous recombinant ligand has been shown to hold considerable promise as a novel large molecule biopharmaceutical therapy. Here, we describe the mechanism of action and discuss potential additional effects of BMP ligand therapy. Bloomsbury Qatar Foundation Journals 2015-11-17 /pmc/articles/PMC4710869/ /pubmed/26779522 http://dx.doi.org/10.5339/gcsp.2015.47 Text en © 2015 Ormiston, Upton, Li, Morrell, licensee Bloomsbury Qatar Foundation Journals. This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Mechanisms of Disease
Ormiston, Mark L.
Upton, Paul D.
Li, Wei
Morrell, Nicholas W.
The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title_full The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title_fullStr The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title_full_unstemmed The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title_short The promise of recombinant BMP ligands and other approaches targeting BMPR-II in the treatment of pulmonary arterial hypertension
title_sort promise of recombinant bmp ligands and other approaches targeting bmpr-ii in the treatment of pulmonary arterial hypertension
topic Mechanisms of Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710869/
https://www.ncbi.nlm.nih.gov/pubmed/26779522
http://dx.doi.org/10.5339/gcsp.2015.47
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