Development and growth trends in angiotensin II-induced murine dissecting abdominal aortic aneurysms

Abstract

Abdominal aortic aneurysms are pathological dilations that can suddenly rupture, causing more than 15,000 deaths in the U.S. annually. Current treatment focuses on observation until an aneurysm's size warrants surgical intervention. Thus, there is a need for therapeutic intervention to inhibit growth of smaller aneurysms. An experimental aneurysm model that infuses angiotensin II into apolipoprotein E‐deficient mice is widely used to investigate underlying pathological mechanisms and potential therapeutics, but this model has two caveats: (1) aneurysms do not always form, and (2) aneurysm severity and growth is inconsistent among animals. Here we use high‐frequency ultrasound to collect data from angiotensin II‐induced aneurysms to develop prediction models of both aneurysm formation and growth. Baseline measurements of aortic diameter, volume/length, and strain were used with animal mass and age in a quadratic discriminant analysis and logistic regression to build two statistical models to predict disease status. Longitudinal ultrasound data were also acquired from mice with aneurysms to quantify aneurysm diameter, circumferential strain, blood flow velocity, aneurysm volume/length, and thrombus and open‐false lumen volumes over 28 days. Measurements taken at aneurysm diagnosis were used with branching artery information to produce a multiple linear regression model to predict final aneurysm volume/length. All three statistical models could be useful in future aneurysm therapeutic studies to better delineate the effects of preventative and suppressive treatments from normal variations in the angiotensin II aneurysm model.

Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition

“…The aneurysmal dissection often has both a true and false lumen, with the false lumen filled with intramural thrombus. While there is some growth after the initial onset, it is modest, and aneurysm typically plateaus in size 13 , 21 . In addition, given its formation and development, the model may better depict an aortic dissection 21 rather than the fusiform aneurysms that are more commonly observed in the human infrarenal abdominal aorta.…”

“…Using a MS550D/MX550D linear transducer (22–50 MHz bandwidth; 40 MHz center frequency, FUJIFILM VisualSonics), long- and short-axis brightness (B-) mode and ECG-gated Kilohertz Visualization (EKV) images of the aorta were acquired, in addition to motion (M-) mode at the proximal, maximum diameter, and distal portions of the infrarenal aorta. Lastly, using a linear step motor, sequential 2D short-axis images were collected to create a 3D ultrasound dataset 13 , 14 .…”

Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture

“…While Angiotensin II (AngII)-induced dissecting aneurysms reproduce several important clinical features of human AAAs, including atherosclerosis, ECM remodeling and inflammation as well as an enhanced propensity for the development of AAAs in male mice, there are also differences compared to human AAAs 8 . Other than human AAAs, mural dissecting AAAs have a suprarenal location, develop within days, show a focal medial tear instead of circumferential medial degradation and form an intramural hematoma by adventitial dissection instead of an intraluminal thrombus 9,10 . Naturally, these differences have to be taken into account, when interpreting the results of the present study.…”

Co-localization of microstructural damage and excessive mechanical strain at aortic branches in angiotensin-II-infused mice

“…AngII-induced lesions not only occur preferentially in the suprarenal aorta of the mouse, they also form on the left side of the suprarenal aorta (Adelsperger et al 2018;Goergen et al 2010b;Xie et al 2012). Several hypotheses have been offered to explain this circumferential specificity (Goergen et al 2011;Goergen et al 2010b), but a clear explanation remains wanting.…”

“…Our continuing search for biomechanical mechanisms must nevertheless build on prior studies. Numerous imaging modalities, including in vivo magnetic resonance imaging, high frequency ultrasound and ex vivo panoramic digital image correlation, have been used to estimate regional biomechanics in the AngII-infused murine abdominal aorta (Adelsperger et al 2018;Favreau et al 2012; Genovese et al 2012;Goergen et al 2011). Biaxial mechanical testing has also shed light on the solid mechanics of the mouse aortic wall prior to and during AngII infusion (Bersi et al 2017;Laroumanie et al 2018).…”