Early pathological characterization of murine dissecting abdominal aortic aneurysms
Autor: | Craig J. Goergen, Abigail Durkes, Adam Lorch, Evan H. Phillips |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty lcsh:Medical technology lcsh:Biotechnology Biomedical Engineering Biophysics Bioengineering 030204 cardiovascular system & hematology Proinflammatory cytokine Biomaterials Extracellular matrix Lesion 03 medical and health sciences 0302 clinical medicine lcsh:TP248.13-248.65 Suprarenal Aorta medicine Aortic dissection Acute aortic syndrome business.industry Articles medicine.disease Angiotensin II 030104 developmental biology lcsh:R855-855.5 cardiovascular system Immunohistochemistry medicine.symptom business |
Zdroj: | APL Bioengineering, Vol 2, Iss 4, Pp 046106-046106-22 (2018) APL Bioengineering |
ISSN: | 2473-2877 |
Popis: | 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. |
Databáze: | OpenAIRE |
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