Wnt2 Contributes to the Development of Atherosclerosis

Atherosclerosis, is a chronic inflammatory disease, characterized by the narrowing of the arteries resulting from the formation of intimal plaques in the wall of arteries. Yet the molecular mechanisms responsible for maintaining the development and progression of atherosclerotic lesions have not bee...

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Autores principales:	Jinyu Zhang, Samuel Rojas, Sanjay Singh, Phillip R. Musich, Matthew Gutierrez, Zhiqiang Yao, Douglas Thewke, Yong Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TGF-β EndMT atherosclerosis Wnt HAECs Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/d937ab11c13c4316809e447aaec0a15b
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id	oai:doaj.org-article:d937ab11c13c4316809e447aaec0a15b
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spelling	oai:doaj.org-article:d937ab11c13c4316809e447aaec0a15b2021-11-30T18:01:43ZWnt2 Contributes to the Development of Atherosclerosis2297-055X10.3389/fcvm.2021.751720https://doaj.org/article/d937ab11c13c4316809e447aaec0a15b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.751720/fullhttps://doaj.org/toc/2297-055XAtherosclerosis, is a chronic inflammatory disease, characterized by the narrowing of the arteries resulting from the formation of intimal plaques in the wall of arteries. Yet the molecular mechanisms responsible for maintaining the development and progression of atherosclerotic lesions have not been fully defined. In this study, we show that TGF-β activates the endothelial-to-mesenchymal transition (EndMT) in cultured human aortic endothelial cells (HAECs) and this transition is dependent on the key executor of the Wnt signaling pathway in vitro. This study presents the first evidence describing the mechanistic details of the TGF-β-induced EndMT signaling pathway in HAECs by documenting the cellular transition to the mesenchymal phenotype including the expression of mesenchymal markers α-SMA and PDGFRα, and the loss of endothelial markers including VE-cadherin and CD31. Furthermore, a short hairpin RNA (shRNA) screening revealed that Wnt2 signaling is required for TGF-β-mediated EndMT of HAECs. Also, we found that LDLR−/− mice fed on a high-fat western-type diet (21% fat, 0.2% cholesterol) expressed high levels of Wnt2 protein in atherosclerotic lesions, confirming that this signaling pathway is involved in atherosclerosis in vivo. These findings suggest that Wnt2 may contribute to atherosclerotic plaque development and this study will render Wnt2 as a potential target for therapeutic intervention aiming at controlling atherosclerosis.Jinyu ZhangJinyu ZhangSamuel RojasSanjay SinghPhillip R. MusichMatthew GutierrezZhiqiang YaoDouglas ThewkeYong JiangFrontiers Media S.A.articleTGF-βEndMTatherosclerosisWntHAECsDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TGF-β EndMT atherosclerosis Wnt HAECs Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	TGF-β EndMT atherosclerosis Wnt HAECs Diseases of the circulatory (Cardiovascular) system RC666-701 Jinyu Zhang Jinyu Zhang Samuel Rojas Sanjay Singh Phillip R. Musich Matthew Gutierrez Zhiqiang Yao Douglas Thewke Yong Jiang Wnt2 Contributes to the Development of Atherosclerosis
description	Atherosclerosis, is a chronic inflammatory disease, characterized by the narrowing of the arteries resulting from the formation of intimal plaques in the wall of arteries. Yet the molecular mechanisms responsible for maintaining the development and progression of atherosclerotic lesions have not been fully defined. In this study, we show that TGF-β activates the endothelial-to-mesenchymal transition (EndMT) in cultured human aortic endothelial cells (HAECs) and this transition is dependent on the key executor of the Wnt signaling pathway in vitro. This study presents the first evidence describing the mechanistic details of the TGF-β-induced EndMT signaling pathway in HAECs by documenting the cellular transition to the mesenchymal phenotype including the expression of mesenchymal markers α-SMA and PDGFRα, and the loss of endothelial markers including VE-cadherin and CD31. Furthermore, a short hairpin RNA (shRNA) screening revealed that Wnt2 signaling is required for TGF-β-mediated EndMT of HAECs. Also, we found that LDLR−/− mice fed on a high-fat western-type diet (21% fat, 0.2% cholesterol) expressed high levels of Wnt2 protein in atherosclerotic lesions, confirming that this signaling pathway is involved in atherosclerosis in vivo. These findings suggest that Wnt2 may contribute to atherosclerotic plaque development and this study will render Wnt2 as a potential target for therapeutic intervention aiming at controlling atherosclerosis.
format	article
author	Jinyu Zhang Jinyu Zhang Samuel Rojas Sanjay Singh Phillip R. Musich Matthew Gutierrez Zhiqiang Yao Douglas Thewke Yong Jiang
author_facet	Jinyu Zhang Jinyu Zhang Samuel Rojas Sanjay Singh Phillip R. Musich Matthew Gutierrez Zhiqiang Yao Douglas Thewke Yong Jiang
author_sort	Jinyu Zhang
title	Wnt2 Contributes to the Development of Atherosclerosis
title_short	Wnt2 Contributes to the Development of Atherosclerosis
title_full	Wnt2 Contributes to the Development of Atherosclerosis
title_fullStr	Wnt2 Contributes to the Development of Atherosclerosis
title_full_unstemmed	Wnt2 Contributes to the Development of Atherosclerosis
title_sort	wnt2 contributes to the development of atherosclerosis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d937ab11c13c4316809e447aaec0a15b
work_keys_str_mv	AT jinyuzhang wnt2contributestothedevelopmentofatherosclerosis AT jinyuzhang wnt2contributestothedevelopmentofatherosclerosis AT samuelrojas wnt2contributestothedevelopmentofatherosclerosis AT sanjaysingh wnt2contributestothedevelopmentofatherosclerosis AT philliprmusich wnt2contributestothedevelopmentofatherosclerosis AT matthewgutierrez wnt2contributestothedevelopmentofatherosclerosis AT zhiqiangyao wnt2contributestothedevelopmentofatherosclerosis AT douglasthewke wnt2contributestothedevelopmentofatherosclerosis AT yongjiang wnt2contributestothedevelopmentofatherosclerosis
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Wnt2 Contributes to the Development of Atherosclerosis

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