Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production
Abstract This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measu...
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Nature Portfolio
2021
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oai:doaj.org-article:326c473fb6a34aa1b1b0159a1e7b9ff62021-12-02T15:56:56ZHeparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production10.1038/s41598-021-90941-w2045-2322https://doaj.org/article/326c473fb6a34aa1b1b0159a1e7b9ff62021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90941-whttps://doaj.org/toc/2045-2322Abstract This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production.Anne Marie W. BartoschRick MathewsMarwa M. MahmoudLimary M. CancelZahin S. HaqJohn M. TarbellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q Anne Marie W. Bartosch Rick Mathews Marwa M. Mahmoud Limary M. Cancel Zahin S. Haq John M. Tarbell Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
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Abstract This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production. |
format |
article |
author |
Anne Marie W. Bartosch Rick Mathews Marwa M. Mahmoud Limary M. Cancel Zahin S. Haq John M. Tarbell |
author_facet |
Anne Marie W. Bartosch Rick Mathews Marwa M. Mahmoud Limary M. Cancel Zahin S. Haq John M. Tarbell |
author_sort |
Anne Marie W. Bartosch |
title |
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
title_short |
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
title_full |
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
title_fullStr |
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
title_full_unstemmed |
Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production |
title_sort |
heparan sulfate proteoglycan glypican-1 and pecam-1 cooperate in shear-induced endothelial nitric oxide production |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/326c473fb6a34aa1b1b0159a1e7b9ff6 |
work_keys_str_mv |
AT annemariewbartosch heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction AT rickmathews heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction AT marwammahmoud heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction AT limarymcancel heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction AT zahinshaq heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction AT johnmtarbell heparansulfateproteoglycanglypican1andpecam1cooperateinshearinducedendothelialnitricoxideproduction |
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