Altered shear stress of blood flow causes plasma membrane damage in endothelial cells

Abstract: The endothelial lining of blood vessels faces many mechanical challenges, including the shear stress (SS) of blood flow, which render it prone to cell membrane ruptures. Such ruptures must be repaired efficiently to maintain cellular integrity and proper vascular function. However, whether...

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Main Authors: Nikita Raj, Chang Pan, Ann Marleen Starke, Anna L. L. Matos, Oliver Soehnlein, Volker Gerke
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Blood Vessels, Thrombosis & Hemostasis
Online Access:http://www.sciencedirect.com/science/article/pii/S2950327224000408
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author Nikita Raj
Chang Pan
Ann Marleen Starke
Anna L. L. Matos
Oliver Soehnlein
Volker Gerke
author_facet Nikita Raj
Chang Pan
Ann Marleen Starke
Anna L. L. Matos
Oliver Soehnlein
Volker Gerke
author_sort Nikita Raj
collection DOAJ
description Abstract: The endothelial lining of blood vessels faces many mechanical challenges, including the shear stress (SS) of blood flow, which render it prone to cell membrane ruptures. Such ruptures must be repaired efficiently to maintain cellular integrity and proper vascular function. However, whether SS of blood flow can indeed affect plasma membrane integrity of endothelial cells and whether any ruptures occurring are repaired is not understood. Here, we show that alterations in the SS of fluid flow induce membrane damage in human endothelial cells, and membrane ruptures increase with increasing shear alterations. Furthermore, we show that inherent SS disturbances at aortic branches in mice are associated with endothelial membrane wounds, which are not observed in regions of laminar flow. We also show that endothelial membrane damages inflicted by shear stress alterations are repaired by a Ca2+-dependent process that involves early endosome exocytosis to provide membrane material for wound closure, suggesting conserved and robust membrane repair responses to endothelial damage in vitro and in vivo. Thus, shear stress alterations, which frequently occur at sites of endothelial dysfunction and before associated pathophysiology, cause membrane wounds in the endothelium, which are repaired efficiently to maintain a functional vasculature.
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series Blood Vessels, Thrombosis & Hemostasis
spelling doaj-art-7a50f91ab3674a429d6e6afb6d853a4a2025-01-26T05:05:31ZengElsevierBlood Vessels, Thrombosis & Hemostasis2950-32722025-02-0121100040Altered shear stress of blood flow causes plasma membrane damage in endothelial cellsNikita Raj0Chang Pan1Ann Marleen Starke2Anna L. L. Matos3Oliver Soehnlein4Volker Gerke5Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, Münster, Germany; Multiscale Imaging Centre, Cells in Motion Interfaculty Center, University of Münster, Münster, Germany; Nikita Raj, Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, 48149 Münster, Germany;Institute of Experimental Pathology, Centre for Molecular Biology of Inflammation, University of Münster, Münster, GermanyInstitute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, Münster, GermanyInstitute of Experimental Pathology, Centre for Molecular Biology of Inflammation, University of Münster, Münster, GermanyInstitute of Experimental Pathology, Centre for Molecular Biology of Inflammation, University of Münster, Münster, GermanyInstitute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, Münster, Germany; Multiscale Imaging Centre, Cells in Motion Interfaculty Center, University of Münster, Münster, Germany; Correspondence: Volker Gerke, Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, 48149 Münster, Germany;Abstract: The endothelial lining of blood vessels faces many mechanical challenges, including the shear stress (SS) of blood flow, which render it prone to cell membrane ruptures. Such ruptures must be repaired efficiently to maintain cellular integrity and proper vascular function. However, whether SS of blood flow can indeed affect plasma membrane integrity of endothelial cells and whether any ruptures occurring are repaired is not understood. Here, we show that alterations in the SS of fluid flow induce membrane damage in human endothelial cells, and membrane ruptures increase with increasing shear alterations. Furthermore, we show that inherent SS disturbances at aortic branches in mice are associated with endothelial membrane wounds, which are not observed in regions of laminar flow. We also show that endothelial membrane damages inflicted by shear stress alterations are repaired by a Ca2+-dependent process that involves early endosome exocytosis to provide membrane material for wound closure, suggesting conserved and robust membrane repair responses to endothelial damage in vitro and in vivo. Thus, shear stress alterations, which frequently occur at sites of endothelial dysfunction and before associated pathophysiology, cause membrane wounds in the endothelium, which are repaired efficiently to maintain a functional vasculature.http://www.sciencedirect.com/science/article/pii/S2950327224000408
spellingShingle Nikita Raj
Chang Pan
Ann Marleen Starke
Anna L. L. Matos
Oliver Soehnlein
Volker Gerke
Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
Blood Vessels, Thrombosis & Hemostasis
title Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
title_full Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
title_fullStr Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
title_full_unstemmed Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
title_short Altered shear stress of blood flow causes plasma membrane damage in endothelial cells
title_sort altered shear stress of blood flow causes plasma membrane damage in endothelial cells
url http://www.sciencedirect.com/science/article/pii/S2950327224000408
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AT annmarleenstarke alteredshearstressofbloodflowcausesplasmamembranedamageinendothelialcells
AT annallmatos alteredshearstressofbloodflowcausesplasmamembranedamageinendothelialcells
AT oliversoehnlein alteredshearstressofbloodflowcausesplasmamembranedamageinendothelialcells
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