Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.

Shear stress induced by laminar blood flow has a profound effect on the morphology and functional phenotype of macrovascular endothelial cells. The influence of laminar flow on the glomerular microvascular endothelium, however, remains largely elusive. The glomerular endothelium, including its glyco...

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Autores principales:	Daan C 't Hart, Johan van der Vlag, Tom Nijenhuis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/79d92ac9fcad446ba1aba23c1003ca20
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spelling	oai:doaj.org-article:79d92ac9fcad446ba1aba23c1003ca202021-11-25T05:54:19ZLaminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.1932-620310.1371/journal.pone.0251129https://doaj.org/article/79d92ac9fcad446ba1aba23c1003ca202021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251129https://doaj.org/toc/1932-6203Shear stress induced by laminar blood flow has a profound effect on the morphology and functional phenotype of macrovascular endothelial cells. The influence of laminar flow on the glomerular microvascular endothelium, however, remains largely elusive. The glomerular endothelium, including its glycocalyx, is a crucial part of the glomerular filtration barrier, which is involved in blood filtration. We therefore investigated the influence of laminar flow-induced shear stress on the glomerular endothelium. Conditionally immortalized mouse glomerular endothelial cells were cultured for 7 days under a laminar flow of 5 dyn/cm2 to mimic the glomerular blood flow. The cells were subsequently analysed for changes in morphology, expression of shear stress-responsive genes, nitric oxide production, glycocalyx composition, expression of anti-oxidant genes and the inflammatory response. Culture under laminar flow resulted in cytoskeletal rearrangement and cell alignment compared to static conditions. Moreover, production of nitric oxide was increased and the expression of the main functional component of the glycocalyx, Heparan Sulfate, was enhanced in response to shear stress. Furthermore, glomerular endothelial cells demonstrated a quiescent phenotype under flow, characterized by a decreased expression of the pro-inflammatory gene ICAM-1 and increased expression of the anti-oxidant enzymes HO-1 and NQO1. Upon exposure to the inflammatory stimulus TNFα, however, glomerular endothelial cells cultured under laminar flow showed an enhanced inflammatory response. In conclusion, laminar flow extensively affects the morphology and functional phenotype of glomerular endothelial cells in culture. Furthermore, glomerular endothelial cells respond differently to shear stress compared to macrovascular endothelium. To improve the translation of future in vitro studies with glomerular endothelial cells to the in vivo situation, it appears therefore crucial to culture glomerular endothelial cells under physiological flow conditions.Daan C 't HartJohan van der VlagTom NijenhuisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251129 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daan C 't Hart Johan van der Vlag Tom Nijenhuis Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
description	Shear stress induced by laminar blood flow has a profound effect on the morphology and functional phenotype of macrovascular endothelial cells. The influence of laminar flow on the glomerular microvascular endothelium, however, remains largely elusive. The glomerular endothelium, including its glycocalyx, is a crucial part of the glomerular filtration barrier, which is involved in blood filtration. We therefore investigated the influence of laminar flow-induced shear stress on the glomerular endothelium. Conditionally immortalized mouse glomerular endothelial cells were cultured for 7 days under a laminar flow of 5 dyn/cm2 to mimic the glomerular blood flow. The cells were subsequently analysed for changes in morphology, expression of shear stress-responsive genes, nitric oxide production, glycocalyx composition, expression of anti-oxidant genes and the inflammatory response. Culture under laminar flow resulted in cytoskeletal rearrangement and cell alignment compared to static conditions. Moreover, production of nitric oxide was increased and the expression of the main functional component of the glycocalyx, Heparan Sulfate, was enhanced in response to shear stress. Furthermore, glomerular endothelial cells demonstrated a quiescent phenotype under flow, characterized by a decreased expression of the pro-inflammatory gene ICAM-1 and increased expression of the anti-oxidant enzymes HO-1 and NQO1. Upon exposure to the inflammatory stimulus TNFα, however, glomerular endothelial cells cultured under laminar flow showed an enhanced inflammatory response. In conclusion, laminar flow extensively affects the morphology and functional phenotype of glomerular endothelial cells in culture. Furthermore, glomerular endothelial cells respond differently to shear stress compared to macrovascular endothelium. To improve the translation of future in vitro studies with glomerular endothelial cells to the in vivo situation, it appears therefore crucial to culture glomerular endothelial cells under physiological flow conditions.
format	article
author	Daan C 't Hart Johan van der Vlag Tom Nijenhuis
author_facet	Daan C 't Hart Johan van der Vlag Tom Nijenhuis
author_sort	Daan C 't Hart
title	Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
title_short	Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
title_full	Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
title_fullStr	Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
title_full_unstemmed	Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
title_sort	laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/79d92ac9fcad446ba1aba23c1003ca20
work_keys_str_mv	AT daancthart laminarflowsubstantiallyaffectsthemorphologyandfunctionalphenotypeofglomerularendothelialcells AT johanvandervlag laminarflowsubstantiallyaffectsthemorphologyandfunctionalphenotypeofglomerularendothelialcells AT tomnijenhuis laminarflowsubstantiallyaffectsthemorphologyandfunctionalphenotypeofglomerularendothelialcells
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Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.

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