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Flow-induced reprogramming of endothelial cells in atherosclerosis
Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success of treatments with cholesterol-lowering drugs and drug-eluting stents, raising the need to identify additional therapeutic targe...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206587/ https://www.ncbi.nlm.nih.gov/pubmed/37225873 http://dx.doi.org/10.1038/s41569-023-00883-1 |
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author | Tamargo, Ian A. Baek, Kyung In Kim, Yerin Park, Christian Jo, Hanjoong |
author_facet | Tamargo, Ian A. Baek, Kyung In Kim, Yerin Park, Christian Jo, Hanjoong |
author_sort | Tamargo, Ian A. |
collection | PubMed |
description | Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success of treatments with cholesterol-lowering drugs and drug-eluting stents, raising the need to identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved and branching arterial regions, where endothelial cells are exposed to disturbed blood flow with characteristic low-magnitude oscillatory shear stress. By contrast, straight arterial regions exposed to stable flow, which is associated with high-magnitude, unidirectional shear stress, are relatively well protected from the disease through shear-dependent, atheroprotective endothelial cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic and metabolic changes in endothelial cells through mechanosensors and mechanosignal transduction pathways. A study using single-cell RNA sequencing and chromatin accessibility analysis in a mouse model of flow-induced atherosclerosis demonstrated that disturbed flow reprogrammes arterial endothelial cells in situ from healthy phenotypes to diseased ones characterized by endothelial inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition and metabolic changes. In this Review, we discuss this emerging concept of disturbed-flow-induced reprogramming of endothelial cells (FIRE) as a potential pro-atherogenic mechanism. Defining the flow-induced mechanisms through which endothelial cells are reprogrammed to promote atherosclerosis is a crucial area of research that could lead to the identification of novel therapeutic targets to combat the high prevalence of atherosclerotic disease. |
format | Online Article Text |
id | pubmed-10206587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102065872023-05-25 Flow-induced reprogramming of endothelial cells in atherosclerosis Tamargo, Ian A. Baek, Kyung In Kim, Yerin Park, Christian Jo, Hanjoong Nat Rev Cardiol Review Article Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success of treatments with cholesterol-lowering drugs and drug-eluting stents, raising the need to identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved and branching arterial regions, where endothelial cells are exposed to disturbed blood flow with characteristic low-magnitude oscillatory shear stress. By contrast, straight arterial regions exposed to stable flow, which is associated with high-magnitude, unidirectional shear stress, are relatively well protected from the disease through shear-dependent, atheroprotective endothelial cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic and metabolic changes in endothelial cells through mechanosensors and mechanosignal transduction pathways. A study using single-cell RNA sequencing and chromatin accessibility analysis in a mouse model of flow-induced atherosclerosis demonstrated that disturbed flow reprogrammes arterial endothelial cells in situ from healthy phenotypes to diseased ones characterized by endothelial inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition and metabolic changes. In this Review, we discuss this emerging concept of disturbed-flow-induced reprogramming of endothelial cells (FIRE) as a potential pro-atherogenic mechanism. Defining the flow-induced mechanisms through which endothelial cells are reprogrammed to promote atherosclerosis is a crucial area of research that could lead to the identification of novel therapeutic targets to combat the high prevalence of atherosclerotic disease. Nature Publishing Group UK 2023-05-24 /pmc/articles/PMC10206587/ /pubmed/37225873 http://dx.doi.org/10.1038/s41569-023-00883-1 Text en © Springer Nature Limited 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Review Article Tamargo, Ian A. Baek, Kyung In Kim, Yerin Park, Christian Jo, Hanjoong Flow-induced reprogramming of endothelial cells in atherosclerosis |
title | Flow-induced reprogramming of endothelial cells in atherosclerosis |
title_full | Flow-induced reprogramming of endothelial cells in atherosclerosis |
title_fullStr | Flow-induced reprogramming of endothelial cells in atherosclerosis |
title_full_unstemmed | Flow-induced reprogramming of endothelial cells in atherosclerosis |
title_short | Flow-induced reprogramming of endothelial cells in atherosclerosis |
title_sort | flow-induced reprogramming of endothelial cells in atherosclerosis |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206587/ https://www.ncbi.nlm.nih.gov/pubmed/37225873 http://dx.doi.org/10.1038/s41569-023-00883-1 |
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