Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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
_version_ 1784720111856254976
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
work_keys_str_mv AT choubliernina exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT taghimeryam exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT menetmarieclaude exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT legallmorgane exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT brucejohanna exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT chafeyphilippe exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT guillonneaufrancois exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT moreauamelie exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT denizotclaire exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT parmentieryannick exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT nakibsamir exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT borderiedidier exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT bouzinbasegardhaniaa exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT couraudpierreolivier exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT bourdouloussandrine exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses
AT declevesxavier exposureofhumancerebralmicrovascularendothelialcellshcmecd3tolaminarshearstressinducesvascularprotectiveresponses