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An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
by
Upton, Paul D.
, Smith, Timothy J.
, Freeman, Adrian
, Ainscough, Alexander J.
, Wharton, John
, Rhodes, Christopher J.
, Whitwell, Harry J.
, Wojciak-Stothard, Beata
, Fellows, Adam
, Gray, Kelly
, Haensel, Maike
, Wilkins, Martin R.
, Vasilaki, Eleni
, Dunmore, Benjamin
, Howard, Luke S.
, Edel, Joshua B.
in
631/1647
/ 631/80
/ 692/420
/ Biochips
/ Biology
/ Biomedical and Life Sciences
/ Blood
/ Bone morphogenetic protein receptor type II
/ Bone Morphogenetic Protein Receptors, Type II - genetics
/ Bone Morphogenetic Protein Receptors, Type II - metabolism
/ Cell interactions
/ Cell proliferation
/ Drug development
/ Endothelial cells
/ Epoprostenol - genetics
/ Epoprostenol - metabolism
/ Gene expression
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypoxia
/ Life Sciences
/ Muscle contraction
/ Oxygenation
/ Phenotypes
/ Prostacyclin
/ Pulmonary Arterial Hypertension - genetics
/ Pulmonary hypertension
/ Signal transduction
/ Smooth muscle
/ SOXF Transcription Factors - genetics
/ SOXF Transcription Factors - metabolism
2022
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An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
by
Upton, Paul D.
, Smith, Timothy J.
, Freeman, Adrian
, Ainscough, Alexander J.
, Wharton, John
, Rhodes, Christopher J.
, Whitwell, Harry J.
, Wojciak-Stothard, Beata
, Fellows, Adam
, Gray, Kelly
, Haensel, Maike
, Wilkins, Martin R.
, Vasilaki, Eleni
, Dunmore, Benjamin
, Howard, Luke S.
, Edel, Joshua B.
in
631/1647
/ 631/80
/ 692/420
/ Biochips
/ Biology
/ Biomedical and Life Sciences
/ Blood
/ Bone morphogenetic protein receptor type II
/ Bone Morphogenetic Protein Receptors, Type II - genetics
/ Bone Morphogenetic Protein Receptors, Type II - metabolism
/ Cell interactions
/ Cell proliferation
/ Drug development
/ Endothelial cells
/ Epoprostenol - genetics
/ Epoprostenol - metabolism
/ Gene expression
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypoxia
/ Life Sciences
/ Muscle contraction
/ Oxygenation
/ Phenotypes
/ Prostacyclin
/ Pulmonary Arterial Hypertension - genetics
/ Pulmonary hypertension
/ Signal transduction
/ Smooth muscle
/ SOXF Transcription Factors - genetics
/ SOXF Transcription Factors - metabolism
2022
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An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
by
Upton, Paul D.
, Smith, Timothy J.
, Freeman, Adrian
, Ainscough, Alexander J.
, Wharton, John
, Rhodes, Christopher J.
, Whitwell, Harry J.
, Wojciak-Stothard, Beata
, Fellows, Adam
, Gray, Kelly
, Haensel, Maike
, Wilkins, Martin R.
, Vasilaki, Eleni
, Dunmore, Benjamin
, Howard, Luke S.
, Edel, Joshua B.
in
631/1647
/ 631/80
/ 692/420
/ Biochips
/ Biology
/ Biomedical and Life Sciences
/ Blood
/ Bone morphogenetic protein receptor type II
/ Bone Morphogenetic Protein Receptors, Type II - genetics
/ Bone Morphogenetic Protein Receptors, Type II - metabolism
/ Cell interactions
/ Cell proliferation
/ Drug development
/ Endothelial cells
/ Epoprostenol - genetics
/ Epoprostenol - metabolism
/ Gene expression
/ Humans
/ Hypertension
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypoxia
/ Life Sciences
/ Muscle contraction
/ Oxygenation
/ Phenotypes
/ Prostacyclin
/ Pulmonary Arterial Hypertension - genetics
/ Pulmonary hypertension
/ Signal transduction
/ Smooth muscle
/ SOXF Transcription Factors - genetics
/ SOXF Transcription Factors - metabolism
2022
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An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
Journal Article
An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
2022
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Overview
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
A biomimetic inducible model of pulmonary arterial hypertension (PAH) is presented, combining natural and induced BMPR2 dysfunction with hypoxia in lung endothelial cells and blood-derived PAH cells to induce smooth muscle activation & proliferation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/80
/ 692/420
/ Biochips
/ Biology
/ Biomedical and Life Sciences
/ Blood
/ Bone morphogenetic protein receptor type II
/ Bone Morphogenetic Protein Receptors, Type II - genetics
/ Bone Morphogenetic Protein Receptors, Type II - metabolism
/ Humans
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypoxia
/ Pulmonary Arterial Hypertension - genetics
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