Dataset Information

Early pathological characterization of murine dissecting abdominal aortic aneurysms.

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.

SUBMITTER: Phillips EH

PROVIDER: S-EPMC6481730 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early pathological characterization of murine dissecting abdominal aortic aneurysms.

Phillips Evan H EH Lorch Adam H AH Durkes Abigail C AC Goergen Craig J CJ

APL bioengineering 20181220 4

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-frequ ...[more]

PMID: 31069328

Similar Datasets

Project description:BACKGROUND:An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors but an important one is size of the aneurysm, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (> 5.5 cm in diameter) are usually operated on; very small AAAs (< 4.0 cm diameter) are monitored with ultrasonography. The optimal timing of surgery would benefit from further evidence. OBJECTIVES:This review compared long-term survival in patients with AAAs of diameter 4.0 to 5.5 cm who received immediate repair versus routine ultrasound surveillance. SEARCH METHODS:For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (February 2012) and CENTRAL (2012, Issue 1). Reference lists of relevant articles were checked for additional studies and the searches were supplemented by handsearches of recent conference proceedings and information from experts in the field. SELECTION CRITERIA:Randomised controlled trials in which men and women with asymptomatic AAAs of diameter 4.0 to 5.5 cm were randomly allocated to immediate repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS:Two authors (GF, MAMM) abstracted the data, which were cross-checked by the other authors (DJB, JTP). Due to the small number of trials, formal tests of heterogeneity and sensitivity analyses were not conducted. MAIN RESULTS:Four trials with a combined total of 3314 patients, the UK Small Aneurysm Trial (UKSAT), the Aneurysm Detection and Management (ADAM) trial, the Comparison of Surveillance Versus Aortic Endografting for Small Aneurysm Repair (CAESAR), and the Positive Impact of Endovascular Options for treating Aneurysms Early (PIVOTAL) fulfilled the inclusion criteria. The four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with surgery) but no significant differences in long-term survival (adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.75 to 1.02, mean follow up 10 years (UKSAT); HR 1.21, 95% CI 0.95 to 1.54, mean follow up 4.9 years (ADAM); HR 0.76, 95% CI 0.30 to 1.93, median follow up 32.4 months (CAESAR); HR 1.01, 95% CI 0.49 to 2.07, mean follow up 20 months (PIVOTAL)). The meta analyses of mortality at one year (CAESAR and PIVOTAL only) and six years (UKSAT and ADAM only) revealed a non-significant association (Peto odds ratio at one year 1.15, 95% CI 0.59 to 2.25; Peto odds ratio at six years 1.11, 95% CI 0.91 to 1.34). AUTHORS' CONCLUSIONS:The results from the four trials to date demonstrate no advantage to early repair (via open or endovascular surgery) for small AAA (4.0 to 5.5 cm) and suggest that 'best care' for these patients favours surveillance. Furthermore, the more recent trials focused on the efficacy of endovascular aneurysm repair and still failed to show benefit. Thus, both open and endovascular repair of small AAAs are not supported by currently available evidence.

Dataset Information

Early pathological characterization of murine dissecting abdominal aortic aneurysms.

Publications

Early pathological characterization of murine dissecting abdominal aortic aneurysms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets