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Optical imaging of MMP-12 active form in inflammation and aneurysm
Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137160/ https://www.ncbi.nlm.nih.gov/pubmed/27917892 http://dx.doi.org/10.1038/srep38345 |
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author | Razavian, Mahmoud Bordenave, Thomas Georgiadis, Dimitris Beau, Fabrice Zhang, Jiasheng Golestani, Reza Toczek, Jakub Jung, Jae-Joon Ye, Yunpeng Kim, Hye-Yeong Han, Jinah Dive, Vincent Devel, Laurent Sadeghi, Mehran M. |
author_facet | Razavian, Mahmoud Bordenave, Thomas Georgiadis, Dimitris Beau, Fabrice Zhang, Jiasheng Golestani, Reza Toczek, Jakub Jung, Jae-Joon Ye, Yunpeng Kim, Hye-Yeong Han, Jinah Dive, Vincent Devel, Laurent Sadeghi, Mehran M. |
author_sort | Razavian, Mahmoud |
collection | PubMed |
description | Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications. |
format | Online Article Text |
id | pubmed-5137160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51371602017-01-27 Optical imaging of MMP-12 active form in inflammation and aneurysm Razavian, Mahmoud Bordenave, Thomas Georgiadis, Dimitris Beau, Fabrice Zhang, Jiasheng Golestani, Reza Toczek, Jakub Jung, Jae-Joon Ye, Yunpeng Kim, Hye-Yeong Han, Jinah Dive, Vincent Devel, Laurent Sadeghi, Mehran M. Sci Rep Article Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications. Nature Publishing Group 2016-12-05 /pmc/articles/PMC5137160/ /pubmed/27917892 http://dx.doi.org/10.1038/srep38345 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Razavian, Mahmoud Bordenave, Thomas Georgiadis, Dimitris Beau, Fabrice Zhang, Jiasheng Golestani, Reza Toczek, Jakub Jung, Jae-Joon Ye, Yunpeng Kim, Hye-Yeong Han, Jinah Dive, Vincent Devel, Laurent Sadeghi, Mehran M. Optical imaging of MMP-12 active form in inflammation and aneurysm |
title | Optical imaging of MMP-12 active form in inflammation and aneurysm |
title_full | Optical imaging of MMP-12 active form in inflammation and aneurysm |
title_fullStr | Optical imaging of MMP-12 active form in inflammation and aneurysm |
title_full_unstemmed | Optical imaging of MMP-12 active form in inflammation and aneurysm |
title_short | Optical imaging of MMP-12 active form in inflammation and aneurysm |
title_sort | optical imaging of mmp-12 active form in inflammation and aneurysm |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137160/ https://www.ncbi.nlm.nih.gov/pubmed/27917892 http://dx.doi.org/10.1038/srep38345 |
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