Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies

Friction caused by blood flowing across cells that line blood vessels (endothelial cells) activates sensors of mechanical force. This produces nitric oxide (NO) which widens placental blood vessels, enabling more blood flow to the baby. This study sought to determine whether the mechanical sensor, P...

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Main Authors: L C Morley, M Debant, H J Gaunt, N A B Simpson, D J Beech
Format: Article
Language:English
Published: Bioscientifica 2023-01-01
Series:Reproduction and Fertility
Subjects:
Online Access:https://raf.bioscientifica.com/view/journals/raf/4/1/RAF-22-0100.xml
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author L C Morley
M Debant
H J Gaunt
N A B Simpson
D J Beech
author_facet L C Morley
M Debant
H J Gaunt
N A B Simpson
D J Beech
author_sort L C Morley
collection DOAJ
description Friction caused by blood flowing across cells that line blood vessels (endothelial cells) activates sensors of mechanical force. This produces nitric oxide (NO) which widens placental blood vessels, enabling more blood flow to the baby. This study sought to determine whether the mechanical sensor, Piezo1, is important for NO production in fetoplacental endothelial cells (FpECs) and whether the steps in this pathway are different in small for gestational age (SGA) babies, where placental blood flow is often altered. We showed that in healthy FpECs, blood flow increased NO signalling. We suggest that in SGA babies, FpECs have an increase in baseline levels of NO signalling, suggestive of a compensatory drive. Treating healthy and SGA cells with a Piezo1 chemical activator, Yoda1, upregulated NO signalling. This shows that Piezo1 is linked to NO and that in SGA, FpECs have the capacity to further increase NO. Further research will establish whether Piezo1 enhancement leads to increased blood flow in the placenta. If so, Piezo1 could be a new target for developing treatments to prevent poor growth of babies in the womb.
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spelling doaj.art-3936b8d22f3d4d38b043fb302c302c7e2023-01-20T06:41:23ZengBioscientificaReproduction and Fertility2633-83862023-01-014113https://doi.org/10.1530/RAF-22-0100Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babiesL C Morley0M Debant1H J Gaunt2N A B Simpson3D J Beech4Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, UK; Academic Department of Obstetrics and Gynaecology, Level 9 Worsley Building, School of Medicine, University of Leeds, Leeds, UK Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, UKLeeds Institute of Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, UKAcademic Department of Obstetrics and Gynaecology, Level 9 Worsley Building, School of Medicine, University of Leeds, Leeds, UKLeeds Institute of Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, UKFriction caused by blood flowing across cells that line blood vessels (endothelial cells) activates sensors of mechanical force. This produces nitric oxide (NO) which widens placental blood vessels, enabling more blood flow to the baby. This study sought to determine whether the mechanical sensor, Piezo1, is important for NO production in fetoplacental endothelial cells (FpECs) and whether the steps in this pathway are different in small for gestational age (SGA) babies, where placental blood flow is often altered. We showed that in healthy FpECs, blood flow increased NO signalling. We suggest that in SGA babies, FpECs have an increase in baseline levels of NO signalling, suggestive of a compensatory drive. Treating healthy and SGA cells with a Piezo1 chemical activator, Yoda1, upregulated NO signalling. This shows that Piezo1 is linked to NO and that in SGA, FpECs have the capacity to further increase NO. Further research will establish whether Piezo1 enhancement leads to increased blood flow in the placenta. If so, Piezo1 could be a new target for developing treatments to prevent poor growth of babies in the womb.https://raf.bioscientifica.com/view/journals/raf/4/1/RAF-22-0100.xmlplacentaendothelial cellspiezo1shear stressnitric oxide
spellingShingle L C Morley
M Debant
H J Gaunt
N A B Simpson
D J Beech
Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
Reproduction and Fertility
placenta
endothelial cells
piezo1
shear stress
nitric oxide
title Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
title_full Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
title_fullStr Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
title_full_unstemmed Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
title_short Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies
title_sort nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of piezo1 mechanosensor in small for gestational age babies
topic placenta
endothelial cells
piezo1
shear stress
nitric oxide
url https://raf.bioscientifica.com/view/journals/raf/4/1/RAF-22-0100.xml
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AT mdebant nitricoxidesynthasephosphorylationinfetoplacentalendotheliumisenhancedbyagonismofpiezo1mechanosensorinsmallforgestationalagebabies
AT hjgaunt nitricoxidesynthasephosphorylationinfetoplacentalendotheliumisenhancedbyagonismofpiezo1mechanosensorinsmallforgestationalagebabies
AT nabsimpson nitricoxidesynthasephosphorylationinfetoplacentalendotheliumisenhancedbyagonismofpiezo1mechanosensorinsmallforgestationalagebabies
AT djbeech nitricoxidesynthasephosphorylationinfetoplacentalendotheliumisenhancedbyagonismofpiezo1mechanosensorinsmallforgestationalagebabies