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Lookup NU author(s): Dr Stephen WhiteORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Local haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response to flow. Suppression of blood flow in zebrafish embryos (by targeting cardiac troponin) reduced EC proliferation in the intersegmental vessels (ISVs) compared to controls exposed to flow. The expression of candidate regulators of proliferation was analysed in EC isolated from zebrafish embryos by qRT-PCR. Genes shown to be expressed in EC were analysed for the ability to regulate proliferation in zebrafish vasculature exposed to flow or no-flow conditions using a knockdown approach. wnk1 negatively regulated proliferation in no-flow conditions, whereas fzd5, gsk3β, trpm7 and bmp2a promoted proliferation in EC exposed to flow. Immunofluorescent staining of mammalian arteries revealed that WNK1 is expressed at sites of low WSS in the murine aorta, and in EC overlying human atherosclerotic plaques. We conclude that WNK1 is expressed in EC at sites of low WSS and in diseased arteries and may influence vascular homeostasis by reducing EC proliferation.
Author(s): Bowley G, Irving S, Hoefer I, Wilkinson R, Pasterkamp G, Darwish HMS, White S, Francis SE, Chico T, Noel E, Serbanovic-Canic J, Evans PC
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2024
Volume: 14
Print publication date: 03/12/2024
Online publication date: 03/12/2024
Acceptance date: 22/10/2024
Date deposited: 16/12/2024
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41598-024-77370-1
DOI: 10.1038/s41598-024-77370-1
Data Access Statement: All data are included within the manuscript or supplementary information files.
PubMed id: 39627337
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