Abstract
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.
Highlights
Aortic rupture is an often fatal consequence of aortic dissections and aneurysms
We found that the aorta expanded and had reduced vessel wall strain regardless of whether a dissecting abdominal aortic aneurysms (AAAs) formed in angiotensin II (AngII)-infused mice
This work advances our understanding of the early development of this murine model and has potential translational significance for improving diagnosis and therapy options of acute aortic syndrome in humans
Summary
Aortic rupture is an often fatal consequence of aortic dissections and aneurysms. The ultimate goal of aortic disease research is to prevent aortic rupture and decrease the high mortality associated with many types of aortic disease. Over the past 20 years, dissecting murine abdominal aortic aneurysms (AAAs) induced via angiotensin II (AngII) have become a valuable model for studying focal aortic dissection and expansion as well as intramural thrombus formation These pathological features are often found in the thoracic aorta of humans with acute aortic syndrome.. The AngII-induced dissecting AAA model has features of atherosclerosis, inflammation, and extracellular matrix (ECM) remodeling, all of which are found in human aortic disease While these have been well studied via histology and molecular analysis at a mature stage, it is difficult to study the early pathology of this model without knowing if and when an animal has already developed a focal dissection and aortic expansion. Some studies have misinterpreted AAA prevalence and possibly overlooked or misidentified aneurysmal lesions depending upon the criteria used
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