Cargando…

Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress

Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximatel...

Descripción completa

Detalles Bibliográficos
Autores principales: White, Stephen J, Hayes, Elaine M, Lehoux, Stéphanie, Jeremy, Jamie Y, Horrevoets, Anton JG, Newby, Andrew C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Subscription Services, Inc., A Wiley Company 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412226/
https://www.ncbi.nlm.nih.gov/pubmed/21302282
http://dx.doi.org/10.1002/jcp.22629
_version_ 1782239939562307584
author White, Stephen J
Hayes, Elaine M
Lehoux, Stéphanie
Jeremy, Jamie Y
Horrevoets, Anton JG
Newby, Andrew C
author_facet White, Stephen J
Hayes, Elaine M
Lehoux, Stéphanie
Jeremy, Jamie Y
Horrevoets, Anton JG
Newby, Andrew C
author_sort White, Stephen J
collection PubMed
description Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm(2)) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15-normal) or 75 dynes/cm(2) (LSS75-elevated). LSS75 upregulated expression of 145 and downregulated expression of 158 genes more than twofold relative to LSS15. Modulation of the metallothioneins (MT1-G, -M, -X) and NADPH oxidase subunits (NOX2, NOX4, NOX5, and p67phox) accompanied suppression of reactive oxygen species production at LSS75. Shear induced changes in dual specificity phosphatases (DUSPs 1, 5, 8, and 16 increasing and DUSPs 6 and 23 decreasing) were observed as well as reduced ERK1/2 but increased p38 MAP kinase phosphorylation. Amongst vasoactive substances, endothelin-1 expression decreased whereas vasoactive intestinal peptide (VIP) and prostacyclin expression increased, despite which intracellular cAMP levels were reduced. Promoter analysis by rVISTA identified a significant over representation of ATF and Nrf2 transcription factor binding sites in genes upregulated by LSS75 compared to LSS15. In summary, LSS75 induced a specific change in behavior, modifying gene expression, reducing ROS levels, altering MAP kinase signaling and reducing cAMP levels, opening multiple avenues for future study. J. Cell. Physiol. 226: 2841–2848, 2011. © 2011 Wiley-Liss, Inc.
format Online
Article
Text
id pubmed-3412226
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Wiley Subscription Services, Inc., A Wiley Company
record_format MEDLINE/PubMed
spelling pubmed-34122262012-08-07 Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress White, Stephen J Hayes, Elaine M Lehoux, Stéphanie Jeremy, Jamie Y Horrevoets, Anton JG Newby, Andrew C J Cell Physiol Original Research Articles Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm(2)) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15-normal) or 75 dynes/cm(2) (LSS75-elevated). LSS75 upregulated expression of 145 and downregulated expression of 158 genes more than twofold relative to LSS15. Modulation of the metallothioneins (MT1-G, -M, -X) and NADPH oxidase subunits (NOX2, NOX4, NOX5, and p67phox) accompanied suppression of reactive oxygen species production at LSS75. Shear induced changes in dual specificity phosphatases (DUSPs 1, 5, 8, and 16 increasing and DUSPs 6 and 23 decreasing) were observed as well as reduced ERK1/2 but increased p38 MAP kinase phosphorylation. Amongst vasoactive substances, endothelin-1 expression decreased whereas vasoactive intestinal peptide (VIP) and prostacyclin expression increased, despite which intracellular cAMP levels were reduced. Promoter analysis by rVISTA identified a significant over representation of ATF and Nrf2 transcription factor binding sites in genes upregulated by LSS75 compared to LSS15. In summary, LSS75 induced a specific change in behavior, modifying gene expression, reducing ROS levels, altering MAP kinase signaling and reducing cAMP levels, opening multiple avenues for future study. J. Cell. Physiol. 226: 2841–2848, 2011. © 2011 Wiley-Liss, Inc. Wiley Subscription Services, Inc., A Wiley Company 2011-11 2011-02-01 /pmc/articles/PMC3412226/ /pubmed/21302282 http://dx.doi.org/10.1002/jcp.22629 Text en Copyright © 2011 Wiley-Liss, Inc. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Research Articles
White, Stephen J
Hayes, Elaine M
Lehoux, Stéphanie
Jeremy, Jamie Y
Horrevoets, Anton JG
Newby, Andrew C
Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title_full Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title_fullStr Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title_full_unstemmed Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title_short Characterization of the Differential Response of Endothelial Cells Exposed to Normal and Elevated Laminar Shear Stress
title_sort characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412226/
https://www.ncbi.nlm.nih.gov/pubmed/21302282
http://dx.doi.org/10.1002/jcp.22629
work_keys_str_mv AT whitestephenj characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress
AT hayeselainem characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress
AT lehouxstephanie characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress
AT jeremyjamiey characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress
AT horrevoetsantonjg characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress
AT newbyandrewc characterizationofthedifferentialresponseofendothelialcellsexposedtonormalandelevatedlaminarshearstress