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TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis

RATIONALE: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress...

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Autores principales: Mahmoud, Marwa M., Kim, Hyejeong Rosemary, Xing, Rouyu, Hsiao, Sarah, Mammoto, Akiko, Chen, Jing, Serbanovic-Canic, Jovana, Feng, Shuang, Bowden, Neil P., Maguire, Richard, Ariaans, Markus, Francis, Sheila E., Weinberg, Peter D., van der Heiden, Kim, Jones, Elizabeth A., Chico, Timothy J.A., Ridger, Victoria, Evans, Paul C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959828/
https://www.ncbi.nlm.nih.gov/pubmed/27245171
http://dx.doi.org/10.1161/CIRCRESAHA.116.308870
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author Mahmoud, Marwa M.
Kim, Hyejeong Rosemary
Xing, Rouyu
Hsiao, Sarah
Mammoto, Akiko
Chen, Jing
Serbanovic-Canic, Jovana
Feng, Shuang
Bowden, Neil P.
Maguire, Richard
Ariaans, Markus
Francis, Sheila E.
Weinberg, Peter D.
van der Heiden, Kim
Jones, Elizabeth A.
Chico, Timothy J.A.
Ridger, Victoria
Evans, Paul C.
author_facet Mahmoud, Marwa M.
Kim, Hyejeong Rosemary
Xing, Rouyu
Hsiao, Sarah
Mammoto, Akiko
Chen, Jing
Serbanovic-Canic, Jovana
Feng, Shuang
Bowden, Neil P.
Maguire, Richard
Ariaans, Markus
Francis, Sheila E.
Weinberg, Peter D.
van der Heiden, Kim
Jones, Elizabeth A.
Chico, Timothy J.A.
Ridger, Victoria
Evans, Paul C.
author_sort Mahmoud, Marwa M.
collection PubMed
description RATIONALE: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. OBJECTIVE: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. METHODS AND RESULTS: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. CONCLUSIONS: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development.
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spelling pubmed-49598282016-08-14 TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis Mahmoud, Marwa M. Kim, Hyejeong Rosemary Xing, Rouyu Hsiao, Sarah Mammoto, Akiko Chen, Jing Serbanovic-Canic, Jovana Feng, Shuang Bowden, Neil P. Maguire, Richard Ariaans, Markus Francis, Sheila E. Weinberg, Peter D. van der Heiden, Kim Jones, Elizabeth A. Chico, Timothy J.A. Ridger, Victoria Evans, Paul C. Circ Res Cellular Biology RATIONALE: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. OBJECTIVE: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. METHODS AND RESULTS: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. CONCLUSIONS: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development. Lippincott Williams & Wilkins 2016-07-22 2016-07-21 /pmc/articles/PMC4959828/ /pubmed/27245171 http://dx.doi.org/10.1161/CIRCRESAHA.116.308870 Text en © 2016 The Authors. Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
spellingShingle Cellular Biology
Mahmoud, Marwa M.
Kim, Hyejeong Rosemary
Xing, Rouyu
Hsiao, Sarah
Mammoto, Akiko
Chen, Jing
Serbanovic-Canic, Jovana
Feng, Shuang
Bowden, Neil P.
Maguire, Richard
Ariaans, Markus
Francis, Sheila E.
Weinberg, Peter D.
van der Heiden, Kim
Jones, Elizabeth A.
Chico, Timothy J.A.
Ridger, Victoria
Evans, Paul C.
TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title_full TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title_fullStr TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title_full_unstemmed TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title_short TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis
title_sort twist1 integrates endothelial responses to flow in vascular dysfunction and atherosclerosis
topic Cellular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959828/
https://www.ncbi.nlm.nih.gov/pubmed/27245171
http://dx.doi.org/10.1161/CIRCRESAHA.116.308870
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