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Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta
Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural endothelial plasma membrane remodelling, but the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142475/ https://www.ncbi.nlm.nih.gov/pubmed/35622139 http://dx.doi.org/10.1007/s00018-022-04362-7 |
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author | Pacia, Marta Z. Chorazy, Natalia Sternak, Magdalena Fels, Benedikt Pacia, Michal Kepczynski, Mariusz Kusche-Vihrog, Kristina Chlopicki, Stefan |
author_facet | Pacia, Marta Z. Chorazy, Natalia Sternak, Magdalena Fels, Benedikt Pacia, Michal Kepczynski, Mariusz Kusche-Vihrog, Kristina Chlopicki, Stefan |
author_sort | Pacia, Marta Z. |
collection | PubMed |
description | Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural endothelial plasma membrane remodelling, but the insight into the mechanism linking these responses is missing. In the present work, we determined the formation of lipid droplets (LDs), nanomechanical, and nanostructural responses in the model of TNF-activated vascular inflammation in the isolated murine aorta using Raman spectroscopy, fluorescence imaging, atomic force microscopy (AFM), and scanning electron microscopy (SEM). We analysed the possible role of Rac1, a major regulator of cytoskeletal organization, in TNF-induced vascular inflammation. We demonstrated that the formation of LDs, polymerization of F-actin, alterations in cortical stiffness, and nanostructural protuberances in endothelial plasma membrane were mediated by the Rac1. In particular, we revealed a significant role for Rac1 in the regulation of the formation of highly unsaturated LDs formed in response to TNF. Inhibition of Rac1 also downregulated the overexpression of ICAM-1 induced by TNF, supporting the role of Rac1 in vascular inflammation. Altogether, our results demonstrate that LDs formation, an integral component of vascular inflammation, is activated by Rac1 that also regulates nanomechanical and nanostructural alterations linked to vascular inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04362-7. |
format | Online Article Text |
id | pubmed-9142475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-91424752022-05-29 Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta Pacia, Marta Z. Chorazy, Natalia Sternak, Magdalena Fels, Benedikt Pacia, Michal Kepczynski, Mariusz Kusche-Vihrog, Kristina Chlopicki, Stefan Cell Mol Life Sci Original Article Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural endothelial plasma membrane remodelling, but the insight into the mechanism linking these responses is missing. In the present work, we determined the formation of lipid droplets (LDs), nanomechanical, and nanostructural responses in the model of TNF-activated vascular inflammation in the isolated murine aorta using Raman spectroscopy, fluorescence imaging, atomic force microscopy (AFM), and scanning electron microscopy (SEM). We analysed the possible role of Rac1, a major regulator of cytoskeletal organization, in TNF-induced vascular inflammation. We demonstrated that the formation of LDs, polymerization of F-actin, alterations in cortical stiffness, and nanostructural protuberances in endothelial plasma membrane were mediated by the Rac1. In particular, we revealed a significant role for Rac1 in the regulation of the formation of highly unsaturated LDs formed in response to TNF. Inhibition of Rac1 also downregulated the overexpression of ICAM-1 induced by TNF, supporting the role of Rac1 in vascular inflammation. Altogether, our results demonstrate that LDs formation, an integral component of vascular inflammation, is activated by Rac1 that also regulates nanomechanical and nanostructural alterations linked to vascular inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04362-7. Springer International Publishing 2022-05-27 2022 /pmc/articles/PMC9142475/ /pubmed/35622139 http://dx.doi.org/10.1007/s00018-022-04362-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Pacia, Marta Z. Chorazy, Natalia Sternak, Magdalena Fels, Benedikt Pacia, Michal Kepczynski, Mariusz Kusche-Vihrog, Kristina Chlopicki, Stefan Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title | Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title_full | Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title_fullStr | Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title_full_unstemmed | Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title_short | Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta |
title_sort | rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by tnf in vascular endothelium in the isolated murine aorta |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142475/ https://www.ncbi.nlm.nih.gov/pubmed/35622139 http://dx.doi.org/10.1007/s00018-022-04362-7 |
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