An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Communications biology - 5(2022), 1 vom: 07. Nov., Seite 1192 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ainscough, Alexander J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.11.2022 Date Revised 08.02.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s42003-022-04169-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348584466 |
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| 100 | 1 | |a Ainscough, Alexander J |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis |
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| 500 | |a Date Revised 08.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a BMPR2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 650 | 7 | |a Bone Morphogenetic Protein Receptors, Type II |2 NLM | |
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| 650 | 7 | |a Epoprostenol |2 NLM | |
| 650 | 7 | |a DCR9Z582X0 |2 NLM | |
| 650 | 7 | |a SOX17 protein, human |2 NLM | |
| 650 | 7 | |a SOXF Transcription Factors |2 NLM | |
| 700 | 1 | |a Smith, Timothy J |e verfasserin |4 aut | |
| 700 | 1 | |a Haensel, Maike |e verfasserin |4 aut | |
| 700 | 1 | |a Rhodes, Christopher J |e verfasserin |4 aut | |
| 700 | 1 | |a Fellows, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Whitwell, Harry J |e verfasserin |4 aut | |
| 700 | 1 | |a Vasilaki, Eleni |e verfasserin |4 aut | |
| 700 | 1 | |a Gray, Kelly |e verfasserin |4 aut | |
| 700 | 1 | |a Freeman, Adrian |e verfasserin |4 aut | |
| 700 | 1 | |a Howard, Luke S |e verfasserin |4 aut | |
| 700 | 1 | |a Wharton, John |e verfasserin |4 aut | |
| 700 | 1 | |a Dunmore, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Upton, Paul D |e verfasserin |4 aut | |
| 700 | 1 | |a Wilkins, Martin R |e verfasserin |4 aut | |
| 700 | 1 | |a Edel, Joshua B |e verfasserin |4 aut | |
| 700 | 1 | |a Wojciak-Stothard, Beata |e verfasserin |4 aut | |
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