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Early pathological characterization of murine dissecting abdominal aortic aneurysms
We report here on the early pathology of a well-established murine model of dissecting abdominal aortic aneurysms (AAAs). Continuous infusion of angiotensin II (AngII) into apolipoprotein E-deficient mice induces the formation of aortic dissection and expansion at some point after implantation of mi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AIP Publishing LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481730/ https://www.ncbi.nlm.nih.gov/pubmed/31069328 http://dx.doi.org/10.1063/1.5053708 |
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author | Phillips, Evan H. Lorch, Adam H. Durkes, Abigail C. Goergen, Craig J. |
author_facet | Phillips, Evan H. Lorch, Adam H. Durkes, Abigail C. Goergen, Craig J. |
author_sort | Phillips, Evan H. |
collection | PubMed |
description | We report here on the early pathology of a well-established murine model of dissecting abdominal aortic aneurysms (AAAs). Continuous infusion of angiotensin II (AngII) into apolipoprotein E-deficient mice induces the formation of aortic dissection and expansion at some point after implantation of miniosmotic pumps containing AngII. While this model has been studied extensively at a chronic stage, we investigated the early pathology of dissecting AAA formation at multiple scales. Using high-frequency ultrasound, we screened 12-week-old male mice daily for initial formation of these aneurysmal lesions between days 3 and 10 post-implantation. We euthanized animals on the day of diagnosis of a dissecting AAA or at day 10 if no aneurysmal lesion developed. Aortic expansion and reduced vessel wall strain occurred in animals regardless of whether a dissecting AAA developed by day 10. The aortas of mice that did not develop dissecting AAAs showed intermediate changes in morphology and biomechanical properties. RNA sequencing and gene expression analysis revealed multiple proinflammatory and matrix remodeling genes to be upregulated in the suprarenal aorta of AngII-infused mice as compared to saline-infused controls. Histology and immunohistochemistry confirmed that extracellular matrix remodeling and inflammatory cell infiltration, notably neutrophils and macrophages, occurred in AngII-infused mice with and without dissecting AAAs but not saline-infused controls. Understanding early disease processes is a critical step forward in translating experimental results in cardiovascular disease research. This work advances our understanding of this well-established murine model with applications for improving early diagnosis and therapy of acute aortic syndrome in humans. |
format | Online Article Text |
id | pubmed-6481730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-64817302019-05-08 Early pathological characterization of murine dissecting abdominal aortic aneurysms Phillips, Evan H. Lorch, Adam H. Durkes, Abigail C. Goergen, Craig J. APL Bioeng Articles We report here on the early pathology of a well-established murine model of dissecting abdominal aortic aneurysms (AAAs). Continuous infusion of angiotensin II (AngII) into apolipoprotein E-deficient mice induces the formation of aortic dissection and expansion at some point after implantation of miniosmotic pumps containing AngII. While this model has been studied extensively at a chronic stage, we investigated the early pathology of dissecting AAA formation at multiple scales. Using high-frequency ultrasound, we screened 12-week-old male mice daily for initial formation of these aneurysmal lesions between days 3 and 10 post-implantation. We euthanized animals on the day of diagnosis of a dissecting AAA or at day 10 if no aneurysmal lesion developed. Aortic expansion and reduced vessel wall strain occurred in animals regardless of whether a dissecting AAA developed by day 10. The aortas of mice that did not develop dissecting AAAs showed intermediate changes in morphology and biomechanical properties. RNA sequencing and gene expression analysis revealed multiple proinflammatory and matrix remodeling genes to be upregulated in the suprarenal aorta of AngII-infused mice as compared to saline-infused controls. Histology and immunohistochemistry confirmed that extracellular matrix remodeling and inflammatory cell infiltration, notably neutrophils and macrophages, occurred in AngII-infused mice with and without dissecting AAAs but not saline-infused controls. Understanding early disease processes is a critical step forward in translating experimental results in cardiovascular disease research. This work advances our understanding of this well-established murine model with applications for improving early diagnosis and therapy of acute aortic syndrome in humans. AIP Publishing LLC 2018-12-20 /pmc/articles/PMC6481730/ /pubmed/31069328 http://dx.doi.org/10.1063/1.5053708 Text en © Author(s). 2473-2877/2018/2(4)/046106/22 All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Articles Phillips, Evan H. Lorch, Adam H. Durkes, Abigail C. Goergen, Craig J. Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title | Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title_full | Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title_fullStr | Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title_full_unstemmed | Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title_short | Early pathological characterization of murine dissecting abdominal aortic aneurysms |
title_sort | early pathological characterization of murine dissecting abdominal aortic aneurysms |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481730/ https://www.ncbi.nlm.nih.gov/pubmed/31069328 http://dx.doi.org/10.1063/1.5053708 |
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