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Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation
Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1(C1039G/+) mouse root/ascending (AS) and descending (DES) aortic...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787454/ https://www.ncbi.nlm.nih.gov/pubmed/31402541 http://dx.doi.org/10.1111/jcmm.14587 |
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author | Emrich, Fabian Penov, Kiril Arakawa, Mamoru Dhablania, Nathan Burdon, Grayson Pedroza, Albert J. Koyano, Tiffany K. Kim, Young M. Raaz, Uwe Connolly, Andrew J. Iosef, Cristiana Fischbein, Michael P. |
author_facet | Emrich, Fabian Penov, Kiril Arakawa, Mamoru Dhablania, Nathan Burdon, Grayson Pedroza, Albert J. Koyano, Tiffany K. Kim, Young M. Raaz, Uwe Connolly, Andrew J. Iosef, Cristiana Fischbein, Michael P. |
author_sort | Emrich, Fabian |
collection | PubMed |
description | Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1(C1039G/+) mouse root/ascending (AS) and descending (DES) aortic samples were examined using DHE staining, lucigenin‐enhanced chemiluminescence (LGCL), Verhoeff's elastin‐Van Gieson staining (elastin breakdown) and in situ zymography for protease activity. Fbn1(C1039G/+) AS‐ or DES‐derived smooth muscle cells (SMC) were treated with anti‐TGF‐β antibody, angiotensin II (AngII), anti‐TGF‐β antibody + AngII, or isotype control. ROS were detected during early aneurysm formation in the Fbn1(C1039G/+) AS aorta, but absent in normal‐sized DES aorta. Fbn1(C1039G/+) mice treated with the unspecific NADPH oxidase inhibitor, apocynin reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ zymography revealed apocynin treatment decreased protease activity. In vitro SMC studies showed Fbn1(C1039G/+)‐derived AS SMC had increased NADPH activity compared to DES‐derived SMC. AS SMC NADPH activity increased with AngII treatment and appeared TGF‐β dependent. In conclusion, ROS play a role in MFS aneurysm development and correspond anatomically with aneurysmal aortic segments. ROS inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII enhances ROS production in MFS AS SMCs and is likely TGF‐β dependent. |
format | Online Article Text |
id | pubmed-6787454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67874542019-10-17 Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation Emrich, Fabian Penov, Kiril Arakawa, Mamoru Dhablania, Nathan Burdon, Grayson Pedroza, Albert J. Koyano, Tiffany K. Kim, Young M. Raaz, Uwe Connolly, Andrew J. Iosef, Cristiana Fischbein, Michael P. J Cell Mol Med Original Articles Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic wall remodelling in MFS, although the mechanism remains unknown. MFS Fbn1(C1039G/+) mouse root/ascending (AS) and descending (DES) aortic samples were examined using DHE staining, lucigenin‐enhanced chemiluminescence (LGCL), Verhoeff's elastin‐Van Gieson staining (elastin breakdown) and in situ zymography for protease activity. Fbn1(C1039G/+) AS‐ or DES‐derived smooth muscle cells (SMC) were treated with anti‐TGF‐β antibody, angiotensin II (AngII), anti‐TGF‐β antibody + AngII, or isotype control. ROS were detected during early aneurysm formation in the Fbn1(C1039G/+) AS aorta, but absent in normal‐sized DES aorta. Fbn1(C1039G/+) mice treated with the unspecific NADPH oxidase inhibitor, apocynin reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ zymography revealed apocynin treatment decreased protease activity. In vitro SMC studies showed Fbn1(C1039G/+)‐derived AS SMC had increased NADPH activity compared to DES‐derived SMC. AS SMC NADPH activity increased with AngII treatment and appeared TGF‐β dependent. In conclusion, ROS play a role in MFS aneurysm development and correspond anatomically with aneurysmal aortic segments. ROS inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII enhances ROS production in MFS AS SMCs and is likely TGF‐β dependent. John Wiley and Sons Inc. 2019-08-11 2019-10 /pmc/articles/PMC6787454/ /pubmed/31402541 http://dx.doi.org/10.1111/jcmm.14587 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Emrich, Fabian Penov, Kiril Arakawa, Mamoru Dhablania, Nathan Burdon, Grayson Pedroza, Albert J. Koyano, Tiffany K. Kim, Young M. Raaz, Uwe Connolly, Andrew J. Iosef, Cristiana Fischbein, Michael P. Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title | Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title_full | Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title_fullStr | Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title_full_unstemmed | Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title_short | Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation |
title_sort | anatomically specific reactive oxygen species production participates in marfan syndrome aneurysm formation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787454/ https://www.ncbi.nlm.nih.gov/pubmed/31402541 http://dx.doi.org/10.1111/jcmm.14587 |
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