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Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm
Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibi...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058712/ https://www.ncbi.nlm.nih.gov/pubmed/33897887 http://dx.doi.org/10.7150/thno.55106 |
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author | Toczek, Jakub Boodagh, Parnaz Sanzida, Nowshin Ghim, Mean Salarian, Mani Gona, Kiran Kukreja, Gunjan Rajendran, Saranya Wei, Linyan Han, Jinah Zhang, Jiasheng Jung, Jae-Joon Graham, Morven Liu, Xinran Sadeghi, Mehran M. |
author_facet | Toczek, Jakub Boodagh, Parnaz Sanzida, Nowshin Ghim, Mean Salarian, Mani Gona, Kiran Kukreja, Gunjan Rajendran, Saranya Wei, Linyan Han, Jinah Zhang, Jiasheng Jung, Jae-Joon Graham, Morven Liu, Xinran Sadeghi, Mehran M. |
author_sort | Toczek, Jakub |
collection | PubMed |
description | Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome. Methods: Uptake of several nanoparticle CT contrast agents was evaluated in a macrophage cell line. The most promising agent, Exitron nano 12000, was further characterized in vitro and used for subsequent in vivo testing. AAA was induced in Apoe(-/-) mice through angiotensin II (Ang II) infusion for up to 4 weeks. Nanoparticle biodistribution and uptake in AAA were evaluated by CT imaging in Ang II-infused Apoe(-/-) mice. After imaging, the aortic tissue was harvested and used from morphometry, transmission electron microscopy and gene expression analysis. A group of Ang II-infused Apoe(-/-) mice underwent nanoparticle-enhanced CT imaging within the first week of Ang II infusion, and their survival and aortic external diameter were evaluated at 4 weeks to address the value of vessel wall CT enhancement in predicting AAA outcome. Results: Exitron nano 12000 showed specific uptake in macrophages in vitro. Nanoparticle accumulation was observed by CT imaging in tissues rich in mononuclear phagocytes. Aortic wall enhancement was detectable on delayed CT images following nanoparticle administration and correlated with vessel wall CD68 expression. Transmission electron microscopy ascertained the presence of nanoparticles in AAA adventitial macrophages. Nanoparticle-induced CT enhancement on images obtained within one week of AAA induction was predictive of AAA outcome at 4 weeks. Conclusions: By establishing the feasibility of CT-based molecular imaging of phagocytic activity in AAA, this study links the inflammatory signal on early time point images to AAA evolution. This readily available technology overcomes an important barrier to cross-sectional, longitudinal and outcome studies, not only in AAA, but also in other cardiovascular pathologies and facilitates the evaluation of modulatory interventions, and ultimately upon clinical translation, patient management. |
format | Online Article Text |
id | pubmed-8058712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-80587122021-04-23 Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm Toczek, Jakub Boodagh, Parnaz Sanzida, Nowshin Ghim, Mean Salarian, Mani Gona, Kiran Kukreja, Gunjan Rajendran, Saranya Wei, Linyan Han, Jinah Zhang, Jiasheng Jung, Jae-Joon Graham, Morven Liu, Xinran Sadeghi, Mehran M. Theranostics Research Paper Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome. Methods: Uptake of several nanoparticle CT contrast agents was evaluated in a macrophage cell line. The most promising agent, Exitron nano 12000, was further characterized in vitro and used for subsequent in vivo testing. AAA was induced in Apoe(-/-) mice through angiotensin II (Ang II) infusion for up to 4 weeks. Nanoparticle biodistribution and uptake in AAA were evaluated by CT imaging in Ang II-infused Apoe(-/-) mice. After imaging, the aortic tissue was harvested and used from morphometry, transmission electron microscopy and gene expression analysis. A group of Ang II-infused Apoe(-/-) mice underwent nanoparticle-enhanced CT imaging within the first week of Ang II infusion, and their survival and aortic external diameter were evaluated at 4 weeks to address the value of vessel wall CT enhancement in predicting AAA outcome. Results: Exitron nano 12000 showed specific uptake in macrophages in vitro. Nanoparticle accumulation was observed by CT imaging in tissues rich in mononuclear phagocytes. Aortic wall enhancement was detectable on delayed CT images following nanoparticle administration and correlated with vessel wall CD68 expression. Transmission electron microscopy ascertained the presence of nanoparticles in AAA adventitial macrophages. Nanoparticle-induced CT enhancement on images obtained within one week of AAA induction was predictive of AAA outcome at 4 weeks. Conclusions: By establishing the feasibility of CT-based molecular imaging of phagocytic activity in AAA, this study links the inflammatory signal on early time point images to AAA evolution. This readily available technology overcomes an important barrier to cross-sectional, longitudinal and outcome studies, not only in AAA, but also in other cardiovascular pathologies and facilitates the evaluation of modulatory interventions, and ultimately upon clinical translation, patient management. Ivyspring International Publisher 2021-04-03 /pmc/articles/PMC8058712/ /pubmed/33897887 http://dx.doi.org/10.7150/thno.55106 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Toczek, Jakub Boodagh, Parnaz Sanzida, Nowshin Ghim, Mean Salarian, Mani Gona, Kiran Kukreja, Gunjan Rajendran, Saranya Wei, Linyan Han, Jinah Zhang, Jiasheng Jung, Jae-Joon Graham, Morven Liu, Xinran Sadeghi, Mehran M. Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title | Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title_full | Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title_fullStr | Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title_full_unstemmed | Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title_short | Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
title_sort | computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058712/ https://www.ncbi.nlm.nih.gov/pubmed/33897887 http://dx.doi.org/10.7150/thno.55106 |
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