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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652052/ https://www.ncbi.nlm.nih.gov/pubmed/34901211 http://dx.doi.org/10.3389/fcvm.2021.751720 |
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author | Zhang, Jinyu Rojas, Samuel Singh, Sanjay Musich, Phillip R. Gutierrez, Matthew Yao, Zhiqiang Thewke, Douglas Jiang, Yong |
author_facet | Zhang, Jinyu Rojas, Samuel Singh, Sanjay Musich, Phillip R. Gutierrez, Matthew Yao, Zhiqiang Thewke, Douglas Jiang, Yong |
author_sort | Zhang, Jinyu |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8652052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86520522021-12-09 Wnt2 Contributes to the Development of Atherosclerosis Zhang, Jinyu Rojas, Samuel Singh, Sanjay Musich, Phillip R. Gutierrez, Matthew Yao, Zhiqiang Thewke, Douglas Jiang, Yong Front Cardiovasc Med Cardiovascular Medicine 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. Frontiers Media S.A. 2021-11-24 /pmc/articles/PMC8652052/ /pubmed/34901211 http://dx.doi.org/10.3389/fcvm.2021.751720 Text en Copyright © 2021 Zhang, Rojas, Singh, Musich, Gutierrez, Yao, Thewke and Jiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Zhang, Jinyu Rojas, Samuel Singh, Sanjay Musich, Phillip R. Gutierrez, Matthew Yao, Zhiqiang Thewke, Douglas Jiang, Yong Wnt2 Contributes to the Development of Atherosclerosis |
title | 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_short | Wnt2 Contributes to the Development of Atherosclerosis |
title_sort | wnt2 contributes to the development of atherosclerosis |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652052/ https://www.ncbi.nlm.nih.gov/pubmed/34901211 http://dx.doi.org/10.3389/fcvm.2021.751720 |
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