Hydrostatic pressure drives sprouting angiogenesis via adherens junction remodelling and YAP signalling.
Autor: | Al-Nuaimi DA; ETH Zürich, DMAVT, Experimental Continuum Mechanics, Zürich, 8092, Switzerland., Rütsche D; Empa, Swiss Federal Laboratories for Materials Science and Technology, Experimental Continuum Mechanics, Dübendorf, 8600, Switzerland., Abukar A; ETH Zürich, DMAVT, Experimental Continuum Mechanics, Zürich, 8092, Switzerland., Hiebert P; Department of Biology, ETH Zürich, Institute of Molecular Health Sciences, 8093, Zürich, Switzerland.; Centre for Biomedicine, Hull York Medical School, The University of Hull, Hull, HU6 7RX, UK., Zanetti D; Department of Biology, ETH Zürich, Institute of Molecular Health Sciences, 8093, Zürich, Switzerland., Cesarovic N; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353, Berlin, Germany.; Department of Health Sciences and Technology, ETH Zürich, 8093, Zürich, Switzerland., Falk V; Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353, Berlin, Germany.; Department of Health Sciences and Technology, ETH Zürich, 8093, Zürich, Switzerland., Werner S; Department of Biology, ETH Zürich, Institute of Molecular Health Sciences, 8093, Zürich, Switzerland., Mazza E; ETH Zürich, DMAVT, Experimental Continuum Mechanics, Zürich, 8092, Switzerland. mazza@imes.mavt.ethz.ch.; Empa, Swiss Federal Laboratories for Materials Science and Technology, Experimental Continuum Mechanics, Dübendorf, 8600, Switzerland. mazza@imes.mavt.ethz.ch., Giampietro C; ETH Zürich, DMAVT, Experimental Continuum Mechanics, Zürich, 8092, Switzerland. costanza.giampietro@empa.ch.; Empa, Swiss Federal Laboratories for Materials Science and Technology, Experimental Continuum Mechanics, Dübendorf, 8600, Switzerland. costanza.giampietro@empa.ch. |
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Jazyk: | angličtina |
Zdroj: | Communications biology [Commun Biol] 2024 Aug 03; Vol. 7 (1), pp. 940. Date of Electronic Publication: 2024 Aug 03. |
DOI: | 10.1038/s42003-024-06604-9 |
Abstrakt: | Endothelial cell physiology is governed by its unique microenvironment at the interface between blood and tissue. A major contributor to the endothelial biophysical environment is blood hydrostatic pressure, which in mechanical terms applies isotropic compressive stress on the cells. While other mechanical factors, such as shear stress and circumferential stretch, have been extensively studied, little is known about the role of hydrostatic pressure in the regulation of endothelial cell behavior. Here we show that hydrostatic pressure triggers partial and transient endothelial-to-mesenchymal transition in endothelial monolayers of different vascular beds. Values mimicking microvascular pressure environments promote proliferative and migratory behavior and impair barrier properties that are characteristic of a mesenchymal transition, resulting in increased sprouting angiogenesis in 3D organotypic model systems ex vivo and in vitro. Mechanistically, this response is linked to differential cadherin expression at the adherens junctions, and to an increased YAP expression, nuclear localization, and transcriptional activity. Inhibition of YAP transcriptional activity prevents pressure-induced sprouting angiogenesis. Together, this work establishes hydrostatic pressure as a key modulator of endothelial homeostasis and as a crucial component of the endothelial mechanical niche. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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