A two-phase response of endothelial cells to hydrostatic pressure

Valeria Prystopiuk; Benedikt Fels; Caroline Sophie Simon; Ivan Liashkovich; Dzmitry Pasrednik; Cornelius Kronlage; Roland Wedlich-Söldner; Hans Oberleithner; Johannes Fels

doi:10.1242/jcs206920

A two-phase response of endothelial cells to hydrostatic pressure

Valeria Prystopiuk, Benedikt Fels, Caroline Sophie Simon, Ivan Liashkovich, Dzmitry Pasrednik, Cornelius Kronlage, Roland Wedlich-Söldner, Hans Oberleithner, Johannes Fels^*

^*Corresponding author for this work

Institute of Physiology

University of Münster

46 Citations (Scopus)

Abstract

The vascular endothelium is exposed to three types of mechanical forces: blood flow-mediated shear stress, vessel diameter-dependent wall tension and hydrostatic pressure. Despite considerable variations of blood pressure during normal and pathological physiology, little is known about the acute molecular and cellular effects of hydrostatic pressure on endothelial cells. Here, we used a combination of quantitative fluorescence microscopy, atomic force microscopy and molecular perturbations to characterize the specific response of endothelial cells to application of pressure. We identified a two-phase response of endothelial cells with an initial response to acute (1 h) application of pressure (100 mmHg) followed by a different response to chronic (24 h) application. While both regimes induce cortical stiffening, the acute response is linked to Ca²⁺-mediated myosin activation, whereas the chronic cell response is dominated by increased cortical actin density and a loss in endothelial barrier function. GsMTx-4 and amiloride inhibit the acute pressure response, which suggests that the ENaC Na⁺ channel is a key player in endothelial pressure sensing. The described two-phase pressure response may participate in the differential effects of transient changes in blood pressure and hypertension.

Original language	English
Article number	jcs206920
Journal	Journal of Cell Science
Volume	131
Issue number	12
ISSN	0021-9533
DOIs	https://doi.org/10.1242/jcs206920
Publication status	Published - 01.06.2018

Funding

We gratefully acknowledge the networking activities of the COST action TD 1002. The authors appreciate the technical support from Jacek Szczerbinski (ETH, Zürich,Switzerland), Marianne Wilhelmi (Institute of Physiology II, University of Münster, Germany), Annette Janning and Ingrid Otto-Valk (Intitute of Cell Dynamics and Imaging, University of Münster, Germany), as well as Thomas Westhoff, Ludger Sasse and Andreas Kolkmann (research workshops, University Hospital Münster, Germany). Work was supported by the Cells-in-Motion Cluster of Excellence, the Program für innovative medizinische Forschung (I-FE 220904 to J.F.) and by the Deutsche Forschungsgemeinschaft (SFB 1009 to R.W.-S., Koselleck-grant OB 63/18 to H.O.).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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10.1242/jcs206920

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title = "A two-phase response of endothelial cells to hydrostatic pressure",

abstract = "The vascular endothelium is exposed to three types of mechanical forces: blood flow-mediated shear stress, vessel diameter-dependent wall tension and hydrostatic pressure. Despite considerable variations of blood pressure during normal and pathological physiology, little is known about the acute molecular and cellular effects of hydrostatic pressure on endothelial cells. Here, we used a combination of quantitative fluorescence microscopy, atomic force microscopy and molecular perturbations to characterize the specific response of endothelial cells to application of pressure. We identified a two-phase response of endothelial cells with an initial response to acute (1 h) application of pressure (100 mmHg) followed by a different response to chronic (24 h) application. While both regimes induce cortical stiffening, the acute response is linked to Ca2+-mediated myosin activation, whereas the chronic cell response is dominated by increased cortical actin density and a loss in endothelial barrier function. GsMTx-4 and amiloride inhibit the acute pressure response, which suggests that the ENaC Na+ channel is a key player in endothelial pressure sensing. The described two-phase pressure response may participate in the differential effects of transient changes in blood pressure and hypertension.",

author = "Valeria Prystopiuk and Benedikt Fels and Simon, \{Caroline Sophie\} and Ivan Liashkovich and Dzmitry Pasrednik and Cornelius Kronlage and Roland Wedlich-S{\"o}ldner and Hans Oberleithner and Johannes Fels",

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AU - Fels, Benedikt

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AU - Pasrednik, Dzmitry

AU - Kronlage, Cornelius

AU - Wedlich-Söldner, Roland

AU - Oberleithner, Hans

AU - Fels, Johannes

N1 - Funding Information: We gratefully acknowledge the networking activities of the COST action TD 1002. The authors appreciate the technical support from Jacek Szczerbinski (ETH, Zürich,Switzerland), Marianne Wilhelmi (Institute of Physiology II, University of Münster, Germany), Annette Janning and Ingrid Otto-Valk (Intitute of Cell Dynamics and Imaging, University of Münster, Germany), as well as Thomas Westhoff, Ludger Sasse and Andreas Kolkmann (research workshops, University Hospital Münster, Germany). Work was supported by the Cells-in-Motion Cluster of Excellence, the Program für innovative medizinische Forschung (I-FE 220904 to J.F.) and by the Deutsche Forschungsgemeinschaft (SFB 1009 to R.W.-S., Koselleck-grant OB 63/18 to H.O.). Publisher Copyright: © 2018. Published by The Company of Biologists Ltd. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/6/1

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N2 - The vascular endothelium is exposed to three types of mechanical forces: blood flow-mediated shear stress, vessel diameter-dependent wall tension and hydrostatic pressure. Despite considerable variations of blood pressure during normal and pathological physiology, little is known about the acute molecular and cellular effects of hydrostatic pressure on endothelial cells. Here, we used a combination of quantitative fluorescence microscopy, atomic force microscopy and molecular perturbations to characterize the specific response of endothelial cells to application of pressure. We identified a two-phase response of endothelial cells with an initial response to acute (1 h) application of pressure (100 mmHg) followed by a different response to chronic (24 h) application. While both regimes induce cortical stiffening, the acute response is linked to Ca2+-mediated myosin activation, whereas the chronic cell response is dominated by increased cortical actin density and a loss in endothelial barrier function. GsMTx-4 and amiloride inhibit the acute pressure response, which suggests that the ENaC Na+ channel is a key player in endothelial pressure sensing. The described two-phase pressure response may participate in the differential effects of transient changes in blood pressure and hypertension.

AB - The vascular endothelium is exposed to three types of mechanical forces: blood flow-mediated shear stress, vessel diameter-dependent wall tension and hydrostatic pressure. Despite considerable variations of blood pressure during normal and pathological physiology, little is known about the acute molecular and cellular effects of hydrostatic pressure on endothelial cells. Here, we used a combination of quantitative fluorescence microscopy, atomic force microscopy and molecular perturbations to characterize the specific response of endothelial cells to application of pressure. We identified a two-phase response of endothelial cells with an initial response to acute (1 h) application of pressure (100 mmHg) followed by a different response to chronic (24 h) application. While both regimes induce cortical stiffening, the acute response is linked to Ca2+-mediated myosin activation, whereas the chronic cell response is dominated by increased cortical actin density and a loss in endothelial barrier function. GsMTx-4 and amiloride inhibit the acute pressure response, which suggests that the ENaC Na+ channel is a key player in endothelial pressure sensing. The described two-phase pressure response may participate in the differential effects of transient changes in blood pressure and hypertension.

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JO - Journal of Cell Science

JF - Journal of Cell Science

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M1 - jcs206920

ER -

A two-phase response of endothelial cells to hydrostatic pressure

Abstract

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