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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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-79d92ac9fcad446ba1aba23c1003ca20 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-79d92ac9fcad446ba1aba23c1003ca202025-08-20T02:55:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025112910.1371/journal.pone.0251129Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells.Daan C 't HartJohan van der VlagTom NijenhuisShear 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0251129&type=printable |
| spellingShingle | Daan C 't Hart Johan van der Vlag Tom Nijenhuis Laminar flow substantially affects the morphology and functional phenotype of glomerular endothelial cells. PLoS ONE |
| title | 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_short | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0251129&type=printable |
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