Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail

Abstract Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of...

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Autores principales:	Marwa M. Mahmoud, Jovana Serbanovic-Canic, Shuang Feng, Celine Souilhol, Rouyu Xing, Sarah Hsiao, Akiko Mammoto, Jing Chen, Markus Ariaans, Sheila E. Francis, Kim Van der Heiden, Victoria Ridger, Paul C. Evans
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d73073520d3c4c1ea3aaec80eeedf382
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spelling	oai:doaj.org-article:d73073520d3c4c1ea3aaec80eeedf3822021-12-02T12:32:29ZShear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail10.1038/s41598-017-03532-z2045-2322https://doaj.org/article/d73073520d3c4c1ea3aaec80eeedf3822017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03532-zhttps://doaj.org/toc/2045-2322Abstract Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.Marwa M. MahmoudJovana Serbanovic-CanicShuang FengCeline SouilholRouyu XingSarah HsiaoAkiko MammotoJing ChenMarkus AriaansSheila E. FrancisKim Van der HeidenVictoria RidgerPaul C. EvansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marwa M. Mahmoud Jovana Serbanovic-Canic Shuang Feng Celine Souilhol Rouyu Xing Sarah Hsiao Akiko Mammoto Jing Chen Markus Ariaans Sheila E. Francis Kim Van der Heiden Victoria Ridger Paul C. Evans Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
description	Abstract Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.
format	article
author	Marwa M. Mahmoud Jovana Serbanovic-Canic Shuang Feng Celine Souilhol Rouyu Xing Sarah Hsiao Akiko Mammoto Jing Chen Markus Ariaans Sheila E. Francis Kim Van der Heiden Victoria Ridger Paul C. Evans
author_facet	Marwa M. Mahmoud Jovana Serbanovic-Canic Shuang Feng Celine Souilhol Rouyu Xing Sarah Hsiao Akiko Mammoto Jing Chen Markus Ariaans Sheila E. Francis Kim Van der Heiden Victoria Ridger Paul C. Evans
author_sort	Marwa M. Mahmoud
title	Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
title_short	Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
title_full	Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
title_fullStr	Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
title_full_unstemmed	Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail
title_sort	shear stress induces endothelial-to-mesenchymal transition via the transcription factor snail
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d73073520d3c4c1ea3aaec80eeedf382
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_version_	1718394065960042496

Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail

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