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Article
Beata Wojciak-Stothard
Imperial College London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6607-7372
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of a disease model representative of the human condition is a key obstacle to the development of new treatments. Here we present a model of PAH, based on a biomimetic pulmonary artery (PA)-on-a-chip, that permits the study of the molecular and functional changes in human pulmonary vascular endothelial and smooth muscle cells in response to triggers of the disease and their response to drugs. We combine natural or induced BMPR2 dysfunction with hypoxia in vascular endothelial cells to trigger smooth muscle activation and proliferation and relate accompanying transcriptomic changes in affected cells to functional effects. Changes in gene expression consistent with observations made in genomic and biochemical studies of the human disease enable insights into underlying disease pathways and mechanisms of drug response. The model offers a novel, promising and more easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
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There is NO Competing Interest. there are no competing interests
This is a list of supplementary files associated with this preprint. Click to download.
- FileS1ListofDEgenesinDisease.SignaturedoublehitHPAECandECFCmodels.xlsx
Supplementary File S1
- FileS3pathwayanalysisofBMPR2independentgenesinHPAECsdoublehitmodel.xlsx
Supplementary File S3
- FileS2BMPR2independentgenelistindoublehitPAHmodel.xlsx
Supplementary File S2
- FileS4alistofHPAECandHPASMCgenesaffectedbyHPAECBMPR2silencing.xlsx
Supplementary File S4
- FileS5pathwayanalysisofhypoxiainducedBMPR2independentgenesinHPASMCsdoublehitmodel.xlsx
Supplementary File S5
- FileS6alistofoverlappinggenesnormoxicADENOvsECFCs.xlsx
Supplementary File S6
- FileS7listofDEgenesinBMPR2deficientECFCandHPASMCs.xlsx
Supplementary File S7
- FileS8pathwayanalysisofhypoxiainducedgenesinECFCsinthedoublehitmodel.xlsx
Supplementary File S8
- FileS9pathwayanalysisofhypoxiainducedgenesinHPASMCsinthedoublehitECFCmodel.xlsx
Supplementary File S9
- FileS10AllDEdatasets.xlsx
Supplementary File S10
- FileS11overlappinggenelistsfromFigure8.xlsx
Supplementary File S11
- FileS12newHPAECOVERLAPMSIGDBPATHWAYSALL.xlsx
Supplementary File S12
- FileS13HPASMCOVERLAPMSIGDBPATHWAYSALL.xlsx
Supplementary File S13
- MicrofluidicmodelPAHSUPPLEMENT.docx
Supplemental Methods, Tables and Figures
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Beata Wojciak-Stothard
Imperial College London
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6607-7372
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 07 Jun, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of a disease model representative of the human condition is a key obstacle to the development of new treatments. Here we present a model of PAH, based on a biomimetic pulmonary artery (PA)-on-a-chip, that permits the study of the molecular and functional changes in human pulmonary vascular endothelial and smooth muscle cells in response to triggers of the disease and their response to drugs. We combine natural or induced BMPR2 dysfunction with hypoxia in vascular endothelial cells to trigger smooth muscle activation and proliferation and relate accompanying transcriptomic changes in affected cells to functional effects. Changes in gene expression consistent with observations made in genomic and biochemical studies of the human disease enable insights into underlying disease pathways and mechanisms of drug response. The model offers a novel, promising and more easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
There is NO Competing Interest. there are no competing interests
This is a list of supplementary files associated with this preprint. Click to download.
- FileS1ListofDEgenesinDisease.SignaturedoublehitHPAECandECFCmodels.xlsx
Supplementary File S1
- FileS3pathwayanalysisofBMPR2independentgenesinHPAECsdoublehitmodel.xlsx
Supplementary File S3
- FileS2BMPR2independentgenelistindoublehitPAHmodel.xlsx
Supplementary File S2
- FileS4alistofHPAECandHPASMCgenesaffectedbyHPAECBMPR2silencing.xlsx
Supplementary File S4
- FileS5pathwayanalysisofhypoxiainducedBMPR2independentgenesinHPASMCsdoublehitmodel.xlsx
Supplementary File S5
- FileS6alistofoverlappinggenesnormoxicADENOvsECFCs.xlsx
Supplementary File S6
- FileS7listofDEgenesinBMPR2deficientECFCandHPASMCs.xlsx
Supplementary File S7
- FileS8pathwayanalysisofhypoxiainducedgenesinECFCsinthedoublehitmodel.xlsx
Supplementary File S8
- FileS9pathwayanalysisofhypoxiainducedgenesinHPASMCsinthedoublehitECFCmodel.xlsx
Supplementary File S9
- FileS10AllDEdatasets.xlsx
Supplementary File S10
- FileS11overlappinggenelistsfromFigure8.xlsx
Supplementary File S11
- FileS12newHPAECOVERLAPMSIGDBPATHWAYSALL.xlsx
Supplementary File S12
- FileS13HPASMCOVERLAPMSIGDBPATHWAYSALL.xlsx
Supplementary File S13
- MicrofluidicmodelPAHSUPPLEMENT.docx
Supplemental Methods, Tables and Figures
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