Morley, LC orcid.org/0000-0002-1109-1396, Debant, M, Gaunt, HJ et al. (2 more authors) (2023) Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies. Reproduction & Fertility, 4 (1). e220100. ISSN 2633-8386
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The authors. Published by Bioscientifica Ltd. This is an open access article 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. |
Keywords: | placenta; endothelial cells; Piezo1; shear stress; nitric oxide |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation RG/17/11/33042 Wellcome Trust 110044/Z/15/Z MRC (Medical Research Council) MR/P002099/1 British Heart Foundation FS/14/22/30734 - H Gaunt |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Jan 2023 16:22 |
Last Modified: | 25 Jun 2023 23:12 |
Status: | Published |
Publisher: | BioScientifica |
Identification Number: | 10.1530/raf-22-0100 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:194917 |