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Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses
Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molec...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164338/ https://www.ncbi.nlm.nih.gov/pubmed/35658915 http://dx.doi.org/10.1186/s12987-022-00344-w |
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author | Choublier, Nina Taghi, Meryam Menet, Marie-Claude Le Gall, Morgane Bruce, Johanna Chafey, Philippe Guillonneau, François Moreau, Amélie Denizot, Claire Parmentier, Yannick Nakib, Samir Borderie, Didier Bouzinba-Segard, Haniaa Couraud, Pierre-Olivier Bourdoulous, Sandrine Declèves, Xavier |
author_facet | Choublier, Nina Taghi, Meryam Menet, Marie-Claude Le Gall, Morgane Bruce, Johanna Chafey, Philippe Guillonneau, François Moreau, Amélie Denizot, Claire Parmentier, Yannick Nakib, Samir Borderie, Didier Bouzinba-Segard, Haniaa Couraud, Pierre-Olivier Bourdoulous, Sandrine Declèves, Xavier |
author_sort | Choublier, Nina |
collection | PubMed |
description | Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood–brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm(−2) SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-022-00344-w. |
format | Online Article Text |
id | pubmed-9164338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91643382022-06-05 Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses Choublier, Nina Taghi, Meryam Menet, Marie-Claude Le Gall, Morgane Bruce, Johanna Chafey, Philippe Guillonneau, François Moreau, Amélie Denizot, Claire Parmentier, Yannick Nakib, Samir Borderie, Didier Bouzinba-Segard, Haniaa Couraud, Pierre-Olivier Bourdoulous, Sandrine Declèves, Xavier Fluids Barriers CNS Research Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood–brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm(−2) SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-022-00344-w. BioMed Central 2022-06-03 /pmc/articles/PMC9164338/ /pubmed/35658915 http://dx.doi.org/10.1186/s12987-022-00344-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Choublier, Nina Taghi, Meryam Menet, Marie-Claude Le Gall, Morgane Bruce, Johanna Chafey, Philippe Guillonneau, François Moreau, Amélie Denizot, Claire Parmentier, Yannick Nakib, Samir Borderie, Didier Bouzinba-Segard, Haniaa Couraud, Pierre-Olivier Bourdoulous, Sandrine Declèves, Xavier Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title | Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title_full | Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title_fullStr | Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title_full_unstemmed | Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title_short | Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses |
title_sort | exposure of human cerebral microvascular endothelial cells hcmec/d3 to laminar shear stress induces vascular protective responses |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164338/ https://www.ncbi.nlm.nih.gov/pubmed/35658915 http://dx.doi.org/10.1186/s12987-022-00344-w |
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